NM_004360.5(CDH1):c.824C>A (p.Ala275Asp) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 15, 2021
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:: RCV002045247.6

Allele description [Variation Report for NM_004360.5(CDH1):c.824C>A (p.Ala275Asp)]

NM_004360.5(CDH1):c.824C>A (p.Ala275Asp)

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.824C>A (p.Ala275Asp)

HGVS:

NC_000016.10:g.68810333C>A
NG_008021.1:g.78042C>A
NM_001317184.2:c.824C>A
NM_001317185.2:c.-792C>A
NM_001317186.2:c.-996C>A
NM_004360.5:c.824C>AMANE SELECT
NP_001304113.1:p.Ala275Asp
NP_004351.1:p.Ala275Asp
LRG_301:g.78042C>A
NC_000016.9:g.68844236C>A

Protein change:

A275D

Links:

dbSNP: rs2152131195

NCBI 1000 Genomes Browser:

rs2152131195

Molecular consequence:

NM_001317185.2:c.-792C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-996C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.824C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.824C>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

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RecName: Full=Ribosomal protein S6 kinase alpha-1; Short=S6K-alpha-1; AltName: F...
RecName: Full=Ribosomal protein S6 kinase alpha-1; Short=S6K-alpha-1; AltName: Full=90 kDa ribosomal protein S6 kinase 1; Short=p90-RSK 1; Short=p90RSK1; Short=p90S6K; AltName: Full=MAP kinase-activated protein kinase 1a; Short=MAPK-activated protein kinase 1a; Short=MAPKAP kinase 1a; Short=MAPKAPK-1a; AltName: Full=Ribosomal S6 kinase 1; Short=RSK-1
gi|20178306|sp|Q15418.2|KS6A1_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002292348	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002292348

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 15, 2021)

germline

clinical testing

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

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

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, SCV002292348.3

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 275 of the CDH1 protein (p.Ala275Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid.

#	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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