NM_004360.5(CDH1):c.2629G>A (p.Gly877Arg) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 29, 2023
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:: RCV000639205.8

Allele description [Variation Report for NM_004360.5(CDH1):c.2629G>A (p.Gly877Arg)]

NM_004360.5(CDH1):c.2629G>A (p.Gly877Arg)

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.2629G>A (p.Gly877Arg)

HGVS:

NC_000016.10:g.68833479G>A
NG_008021.1:g.101188G>A
NM_001317184.2:c.2446G>A
NM_001317185.2:c.1081G>A
NM_001317186.2:c.664G>A
NM_004360.5:c.2629G>AMANE SELECT
NP_001304113.1:p.Gly816Arg
NP_001304114.1:p.Gly361Arg
NP_001304115.1:p.Gly222Arg
NP_004351.1:p.Gly877Arg
LRG_301t1:c.2629G>A
LRG_301:g.101188G>A
NC_000016.9:g.68867382G>A
NM_004360.3:c.2629G>A
NM_004360.4:c.2629G>A

Protein change:

G222R

Links:

dbSNP: rs555842031

NCBI 1000 Genomes Browser:

rs555842031

Molecular consequence:

NM_001317184.2:c.2446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317186.2:c.664G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.2629G>A - 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

Recent activity

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ethylene-responsive transcription factor ERF110-like [Cucumis melo]
ethylene-responsive transcription factor ERF110-like [Cucumis melo]
gi|659116128|ref|XP_008457918.1|

Protein
putative lipase isoform X3 [Cucumis melo var. makuwa]
putative lipase isoform X3 [Cucumis melo var. makuwa]
gi|1735215241|gb|KAA0057035.1||gnl| STE|E6C27_scaffold96G002210

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000760774	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30287823, 33322525, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000760774

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 29, 2023)

germline

clinical testing

PubMed (3)
[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

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status.

Marwitz T, Hüneburg R, Spier I, Lau JF, Kristiansen G, Lingohr P, Kalff JC, Aretz S, Nattermann J, Strassburg CP.

Cancers (Basel). 2020 Dec 11;12(12). doi:pii: E3726. 10.3390/cancers12123726.

PubMed [citation]

PMID:: 33322525
PMCID:: PMC7763201

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000760774.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 877 of the CDH1 protein (p.Gly877Arg). This variant is present in population databases (rs555842031, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer and/or clinical features of hereditary diffuse gastric cancer (PMID: 30287823, 33322525). ClinVar contains an entry for this variant (Variation ID: 423788). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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