VCV001412663.9 - ClinVar

NC_000001.10:g.(?_861322)_(3768971_?)del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(6)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000001.10:g.(?_861322)_(3768971_?)del

Variation ID: 1412663 Accession: VCV001412663.9

Type and length

Deletion, 2,907,650 bp

Location

Cytogenetic: 1p36.33-36.32 1: 861322-3768971 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 28, 2022	Nov 11, 2023	Oct 17, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000001.10:g.(?_861322)_(3768971_?)del

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GNB1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	313	477
SKI		No evidence available	No evidence available	GRCh38 GRCh37	1110	1257
TP73		No evidence available	No evidence available	GRCh38 GRCh37	58	170
ACAP3	-	-	-	GRCh38 GRCh37	62	214
ACTRT2		-	-	GRCh38 GRCh37	30	170
AGRN		-	-	GRCh38 GRCh37	2102	2378
ANKRD65	-	-	-	GRCh38 GRCh37	28	212
ARHGEF16		-	-	GRCh38 GRCh37	68	182
ATAD3A		-	-	GRCh38 GRCh37	297	467
ATAD3B		-	-	GRCh38 GRCh37	105	281

There are 66 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001919159.7
Combined immunodeficiency due to OX40 deficiency	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001919158.7
Peroxisome biogenesis disorder, complementation group 7	Pathogenic (1)	criteria provided, single submitter	Oct 17, 2022	RCV001919157.5
Ehlers-Danlos syndrome, spondylodysplastic type, 2 Spondyloepimetaphyseal dysplasia with joint laxity	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001923367.9
not provided	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001943250.4
Joubert syndrome 25	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001923368.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Peroxisome biogenesis disorder, complementation group 7 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002244419.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (3) PubMed: 9683594‚ 10862081‚ 21031596 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the PEX10 gene has been identified. Loss-of-function variants in PEX10 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the PEX10 gene has been identified. Loss-of-function variants in PEX10 are known to be pathogenic (PMID: 9683594, 10862081, 21031596). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with PEX10-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Uncertain significance (Nov 26, 2021)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV002275296 appears to (...more) Source: NCBI	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002275296.1 First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022	Publications: PubMed (1) PubMed: 31674007 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the GNB1 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the GNB1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GNB1 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of GNB1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 31674007). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Sep 19, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV002207737 appears to (...more) Source: NCBI	Combined immunodeficiency due to OX40 deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002207737.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Comment: A gross deletion of the genomic region encompassing the full coding sequence of the TNFRSF4 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the TNFRSF4 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNFRSF4 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with TNFRSF4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Sep 19, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV002213876 appears to (...more) Source: NCBI	Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002213876.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Comment: A gross deletion of the genomic region encompassing the full coding sequence of the ISG15 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the ISG15 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ISG15 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with ISG15-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Pathogenic (Oct 17, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV002244562 appears to (...more) Source: NCBI	Joubert syndrome 25 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002244562.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 26477546 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the CEP104 gene has been identified. Loss-of-function variants in CEP104 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the CEP104 gene has been identified. Loss-of-function variants in CEP104 are known to be pathogenic (PMID: 26477546). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with CEP104-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Uncertain significance (Oct 17, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV002179189 appears to (...more) Source: NCBI	Ehlers-Danlos syndrome, spondylodysplastic type, 2 Spondyloepimetaphyseal dysplasia with joint laxity Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002179189.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 19492091 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the B3GALT6 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the B3GALT6 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in B3GALT6 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of B3GALT6 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 19492091). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the PEX10 gene has been identified. Loss-of-function variants in PEX10 are known to be pathogenic (PMID: 9683594, 10862081, 21031596). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with PEX10-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the GNB1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GNB1 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of GNB1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 31674007). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the TNFRSF4 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNFRSF4 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with TNFRSF4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the ISG15 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ISG15 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with ISG15-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the CEP104 gene has been identified. Loss-of-function variants in CEP104 are known to be pathogenic (PMID: 26477546). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with CEP104-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the B3GALT6 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in B3GALT6 cause disease. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of B3GALT6 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 19492091). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.	Wu H	Clinical genetics	2020	PMID: 31674007
Joubert Syndrome in French Canadians and Identification of Mutations in CEP104.	Srour M	American journal of human genetics	2015	PMID: 26477546
Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.	Ebberink MS	Human mutation	2011	PMID: 21031596
Gene-network analysis identifies susceptibility genes related to glycobiology in autism.	van der Zwaag B	PloS one	2009	PMID: 19492091
Phenotype-genotype relationships in PEX10-deficient peroxisome biogenesis disorder patients.	Warren DS	Human mutation	2000	PMID: 10862081
Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders.	Warren DS	American journal of human genetics	1998	PMID: 9683594

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000001.10:g.(?_861322)_(3768971_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...