VCV001452047.4 - ClinVar

NC_000018.9:g.(?_2847807)_(3582246_?)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.

(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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000018.9:g.(?_2847807)_(3582246_?)del

Variation ID: 1452047 Accession: VCV001452047.4

Type and length

Deletion, 734,440 bp

Location

Cytogenetic: 18p11.32-11.31 18: 2847807-3582246 (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	Sep 28, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000018.9:g.(?_2847807)_(3582246_?)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.
TGIF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	153	295
DLGAP1		-	-	GRCh38 GRCh37	60	240
EMILIN2		-	-	GRCh38 GRCh37	115	305
LPIN2		-	-	GRCh38 GRCh37	893	1046
MYL12A	-	-	-	GRCh38 GRCh37	7	155
MYL12B		-	-	GRCh38 GRCh37	1	148
MYOM1		-	-	GRCh38 GRCh37	1759	1913

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.
Holoprosencephaly 4	Pathogenic (1)	criteria provided, single submitter	Sep 28, 2022	RCV001994471.5

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 (Sep 28, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Holoprosencephaly 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002230557.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (5) PubMed: 16962354‚ 22125506‚ 16199538‚ 17001671‚ 19431187 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the TGIF1 gene has been identified. Loss-of-function variants in TGIF1 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the TGIF1 gene has been identified. Loss-of-function variants in TGIF1 are known to be pathogenic (PMID: 16962354, 22125506). 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 TGIF1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 16199538, 17001671, 19431187, 22125506). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the TGIF1 gene has been identified. Loss-of-function variants in TGIF1 are known to be pathogenic (PMID: 16962354, 22125506). 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 TGIF1 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 16199538, 17001671, 19431187, 22125506). For these reasons, this variant has been classified as Pathogenic.

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
TGIF Mutations in Human Holoprosencephaly: Correlation between Genotype and Phenotype.	Keaton AA	Molecular syndromology	2010	PMID: 22125506
Array-CGH analysis indicates a high prevalence of genomic rearrangements in holoprosencephaly: an updated map of candidate loci.	Bendavid C	Human mutation	2009	PMID: 19431187
Functional analysis of mutations in TGIF associated with holoprosencephaly.	El-Jaick KB	Molecular genetics and metabolism	2007	PMID: 16962354
Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex: association with an 18p11.3 deletion.	Kantaputra PN	American journal of medical genetics. Part A	2006	PMID: 17001671
Multicolour FISH and quantitative PCR can detect submicroscopic deletions in holoprosencephaly patients with a normal karyotype.	Bendavid C	Journal of medical genetics	2006	PMID: 16199538

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000018.9:g.(?_2847807)_(3582246_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...