VCV001457416.4 - ClinVar

NC_000003.11:g.(?_93593089)_(93845334_?)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_000003.11:g.(?_93593089)_(93845334_?)del

Variation ID: 1457416 Accession: VCV001457416.4

Type and length

Deletion, 252,246 bp

Location

Cytogenetic: 3q11.1 3: 93593089-93845334 (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	Jun 9, 2024	Jun 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000003.11:g.(?_93593089)_(93845334_?)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.
ARL13B		-	-	GRCh38 GRCh37	332	381
DHFR2		-	-	GRCh38 GRCh37	-	23
NSUN3		-	-	GRCh38 GRCh37	88	110
PROS1		-	-	GRCh38 GRCh37	482	511
STX19	-	-	-	GRCh38 GRCh37	-	44

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.
Thrombophilia due to protein S deficiency, autosomal recessive	Pathogenic (1)	criteria provided, single submitter	Jun 20, 2023	RCV001953740.5

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 (Jun 20, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Thrombophilia due to protein S deficiency, autosomal recessive Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002240536.4 First in ClinVar: Mar 28, 2022 Last updated: Jun 09, 2024	Publications: PubMed (3) PubMed: 16363235‚ 22627709‚ 9241758 Comment: For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with protein S deficiency (PMID: … (more) For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with protein S deficiency (PMID: 16363235, 22627709). A gross deletion of the genomic region encompassing the full coding sequence of the PROS1 gene has been identified. Loss-of-function variants in PROS1 are known to be pathogenic (PMID: 9241758). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. A similar copy number variant has been observed in individual(s) with protein S deficiency (PMID: 16363235, 22627709). A gross deletion of the genomic region encompassing the full coding sequence of the PROS1 gene has been identified. Loss-of-function variants in PROS1 are known to be pathogenic (PMID: 9241758). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.

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
Small and large PROS1 deletions but no other types of rearrangements detected in patients with protein S deficiency.	Lind-Halldén C	Thrombosis and haemostasis	2012	PMID: 22627709
Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency.	Johansson AM	Thrombosis and haemostasis	2005	PMID: 16363235
Protein S deficiency: a database of mutations. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.	Gandrille S	Thrombosis and haemostasis	1997	PMID: 9241758

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000003.11:g.(?_93593089)_(93845334_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...