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NM_004360.5(CDH1):c.1613A>T (p.Asp538Val) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 17, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000198874.9

Allele description [Variation Report for NM_004360.5(CDH1):c.1613A>T (p.Asp538Val)]

NM_004360.5(CDH1):c.1613A>T (p.Asp538Val)

Gene:
CDH1:cadherin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_004360.5(CDH1):c.1613A>T (p.Asp538Val)
HGVS:
  • NC_000016.10:g.68819327A>T
  • NG_008021.1:g.87036A>T
  • NM_001317184.2:c.1430A>T
  • NM_001317185.2:c.65A>T
  • NM_001317186.2:c.-254-2674A>T
  • NM_004360.5:c.1613A>TMANE SELECT
  • NP_001304113.1:p.Asp477Val
  • NP_001304114.1:p.Asp22Val
  • NP_004351.1:p.Asp538Val
  • LRG_301t1:c.1613A>T
  • LRG_301:g.87036A>T
  • NC_000016.9:g.68853230A>T
  • NM_004360.3:c.1613A>T
  • NM_004360.5(CDH1):c.1613A>TMANE SELECT
  • p.Asp538Val
Protein change:
D22V
Links:
dbSNP: rs863224726
NCBI 1000 Genomes Browser:
rs863224726
Molecular consequence:
  • NM_001317186.2:c.-254-2674A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001317184.2:c.1430A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317185.2:c.65A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1613A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:
Hereditary diffuse gastric cancer
Identifiers:
MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000254814Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 17, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000254814.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 216589). This missense change has been observed in individuals with clinical features of hereditary diffuse gastric and lobular breast cancer syndrome (Invitae; external communication). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 538 of the CDH1 protein (p.Asp538Val).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024