VCV000692221.1 - ClinVar

NC_000001.11:g.145601946_148597425del

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.

(1)

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.

Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000001.11:g.145601946_148597425del

Variation ID: 692221 Accession: VCV000692221.1

Type and length

Deletion, 2,995,480 bp

Location

Cytogenetic: 1q21.1-21.2 1: 145601946-148597425 (GRCh38) [ 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	Nov 2, 2019	Nov 2, 2019	Sep 16, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NC_000001.11:g.145601946_148597425del

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.

protein loss of function; Variation Ontology [ VariO:0043]

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.
GJA5		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	220	579
GJA8		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	259	549
CHD1L		No evidence available	No evidence available	GRCh38 GRCh37	176	560
ACP6		-	-	GRCh38 GRCh37	37	327
ANKRD34A	-	-	-	GRCh38 GRCh37	22	229
ANKRD35	-	-	-	GRCh38 GRCh37	85	290
BCL9		-	-	GRCh38 GRCh37	144	434
CD160		-	-	GRCh38 GRCh37	10	229
CH17-408M7.1	-	-	-	GRCh38	-	55
FMO5		-	-	GRCh38 GRCh37	-	353

There are 115 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

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.
Radial aplasia-thrombocytopenia syndrome	Likely pathogenic (1)	no assertion criteria provided	Sep 16, 2019	RCV000853559.1

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.
Likely pathogenic (Sep 16, 2019)	no assertion criteria provided Method: research	Radial aplasia-thrombocytopenia syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Clinical Genetics Branch, National Institutes of Health Accession: SCV000995057.1 First in ClinVar: Nov 02, 2019 Last updated: Nov 02, 2019	Comment: The 1q21.1 TAR-associated deletion in combination with the G variant of rs61746197 on the non-deleted allele is associated with a TAR-like phenotype. rs61746197 G could … (more) The 1q21.1 TAR-associated deletion in combination with the G variant of rs61746197 on the non-deleted allele is associated with a TAR-like phenotype. rs61746197 G could be a functional enhancer/repressor element but more studies are required to identify the specific factor(s) responsible. Overall, our findings suggest a role of rs61746197 A>G and human disease in the setting of a 1q21.1 deletion on the other chromosome. (less) Clinical Features: Absent radius (present) , TAR-like (present)

Comment:

The 1q21.1 TAR-associated deletion in combination with the G variant of rs61746197 on the non-deleted allele is associated with a TAR-like phenotype. rs61746197 G could be a functional enhancer/repressor element but more studies are required to identify the specific factor(s) responsible. Overall, our findings suggest a role of rs61746197 A>G and human disease in the setting of a 1q21.1 deletion on the other chromosome.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
protein loss of function (VariO:0043)	Method not provided	Result not provided	Clinical Genetics Branch, National Institutes of Health Accession: SCV000995057.1

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
1q21.1 deletion and a rare functional polymorphism in siblings with thrombocytopenia-absent radius-like phenotypes.	Brodie SA	Cold Spring Harbor molecular case studies	2019	PMID: 31836590

Text-mined citations for this variant ...

Record last updated Nov 20, 2023

ClinVar Genomic variation as it relates to human health

NC_000001.11:g.145601946_148597425del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...