VCV000619019.4 - ClinVar

NC_000002.12:g.47142010_47142443dup

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 benign

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000002.12:g.47142010_47142443dup

Variation ID: 619019 Accession: VCV000619019.4

Type and length

Duplication, 434 bp

Location

Cytogenetic: 2p21 2: 47142010-47142443 (GRCh38) [ NCBI UCSC ] 2: 47369148-47369581 (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	Feb 23, 2019	Oct 7, 2023	May 17, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NC_000002.12:g.47142010_47142443dup
NC_000002.11:g.(?_47369148)_(47369581_?)dup

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.
EPCAM		-	-	GRCh38 GRCh37	772	876
STPG4	-	-	-	GRCh38 GRCh37	1	24

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.
Lynch syndrome	Likely benign (1)	criteria provided, single submitter	May 17, 2018	RCV000757934.4

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 benign (May 17, 2018)	criteria provided, single submitter (Tsai GJ et al. (Genet Med 2018)) Method: research	Lynch syndrome (Autosomal dominant inheritance) Affected status: no Allele origin: germline	University of Washington Department of Laboratory Medicine, University of Washington Accession: SCV000886462.2 First in ClinVar: Feb 23, 2019 Last updated: Oct 07, 2023	Publications: PubMed (1) PubMed: 30374176 Comment: The variant known as the EPCAM exon 1 duplication was previously classified as a variant of uncertain significance is now classified as likely benign. Family … (more) The variant known as the EPCAM exon 1 duplication was previously classified as a variant of uncertain significance is now classified as likely benign. Family cosegregation analysis was performed on one observed family using analyze.myvariant.org (RaÃ±ola et al, 2018, PMID:28965303) and shows a likelihood ratio of 0.14 to 1 that this allele explains Lynch syndrome cancers in the family (Thompson et al., 2003. PMID:290079). Computational predictions also suggest the EPCAM exon 1 duplication is benign. Together, this information is not consistent with a pathogenic mutation in EPCAM. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives less than 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter EPCAM function or modify risk for Lynch syndrome. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. (less) Family history: yes

Comment:

The variant known as the EPCAM exon 1 duplication was previously classified as a variant of uncertain significance is now classified as likely benign. Family cosegregation analysis was performed on one observed family using analyze.myvariant.org (RaÃ±ola et al, 2018, PMID:28965303) and shows a likelihood ratio of 0.14 to 1 that this allele explains Lynch syndrome cancers in the family (Thompson et al., 2003. PMID:290079). Computational predictions also suggest the EPCAM exon 1 duplication is benign. Together, this information is not consistent with a pathogenic mutation in EPCAM. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives less than 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter EPCAM function or modify risk for Lynch syndrome. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NC_000002.12:g.47142010_47142443dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...