NM_004360.5(CDH1):c.203A>G (p.Tyr68Cys) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 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:: RCV001216703.6

Allele description [Variation Report for NM_004360.5(CDH1):c.203A>G (p.Tyr68Cys)]

NM_004360.5(CDH1):c.203A>G (p.Tyr68Cys)

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.203A>G (p.Tyr68Cys)

HGVS:

NC_000016.10:g.68801709A>G
NG_008021.1:g.69418A>G
NM_001317184.2:c.203A>G
NM_001317185.2:c.-1413A>G
NM_001317186.2:c.-1617A>G
NM_004360.5:c.203A>GMANE SELECT
NP_001304113.1:p.Tyr68Cys
NP_004351.1:p.Tyr68Cys
LRG_301t1:c.203A>G
LRG_301:g.69418A>G
NC_000016.9:g.68835612A>G
NM_004360.3:c.203A>G
NM_004360.4:c.203A>G

Protein change:

Y68C

Links:

dbSNP: rs1284989530

NCBI 1000 Genomes Browser:

rs1284989530

Molecular consequence:

NM_001317185.2:c.-1413A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1617A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.203A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.203A>G - 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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RPL36AP36 ribosomal protein L36a pseudogene 36 [Homo sapiens]
RPL36AP36 ribosomal protein L36a pseudogene 36 [Homo sapiens]
Gene ID:644834

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001388513	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32318955, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001388513

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Evaluation of pathogenetic mutations in breast cancer predisposition genes in population-based studies conducted among Chinese women.

Zeng C, Guo X, Wen W, Shi J, Long J, Cai Q, Shu XO, Xiang Y, Zheng W.

Breast Cancer Res Treat. 2020 Jun;181(2):465-473. doi: 10.1007/s10549-020-05643-0. Epub 2020 Apr 21.

PubMed [citation]

PMID:: 32318955
PMCID:: PMC7188717

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001388513.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 820574). This missense change has been observed in individual(s) with breast cancer (PMID: 32318955). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 68 of the CDH1 protein (p.Tyr68Cys).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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