NM_004360.5(CDH1):c.2602C>A (p.Arg868Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 12, 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:: RCV001799514.6

Allele description [Variation Report for NM_004360.5(CDH1):c.2602C>A (p.Arg868Ser)]

NM_004360.5(CDH1):c.2602C>A (p.Arg868Ser)

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.2602C>A (p.Arg868Ser)

HGVS:

NC_000016.10:g.68833452C>A
NG_008021.1:g.101161C>A
NM_001317184.2:c.2419C>A
NM_001317185.2:c.1054C>A
NM_001317186.2:c.637C>A
NM_004360.5:c.2602C>AMANE SELECT
NP_001304113.1:p.Arg807Ser
NP_001304114.1:p.Arg352Ser
NP_001304115.1:p.Arg213Ser
NP_004351.1:p.Arg868Ser
LRG_301t1:c.2602C>A
LRG_301:g.101161C>A
NC_000016.9:g.68867355C>A
NM_004360.3:c.2602C>A
NM_004360.4:c.2602C>A

Protein change:

R213S

Links:

dbSNP: rs864622630

NCBI 1000 Genomes Browser:

rs864622630

Molecular consequence:

NM_001317184.2:c.2419C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.1054C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317186.2:c.637C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.2602C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Name:: Blepharocheilodontic syndrome 1 (BCDS1)
Identifiers:: MONDO: MONDO:0054740; MedGen: C4551988; Orphanet: 1997; OMIM: 119580

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

Name:: Malignant tumor of prostate
Synonyms:: Prostate cancer
Identifiers:: MONDO: MONDO:0008315; MedGen: C0376358; Orphanet: 1331; Human Phenotype Ontology: HP:0012125

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002043756	Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 12, 2021)	unknown	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

SCV002043756

Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 12, 2021)

unknown

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	unknown	yes	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology, SCV002043756.1

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

Description

The c.2602C>A variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD). The variant is not present in Indian Exome Database and in our in-house exome database. The variant was earlier reported to ClinVar (Accession: VCV000220695.10) several times as uncertain significance in association with hereditary cancer predisposing syndrome. CDH1 Arg868Cys occurs at a position that is conserved across species and there is a large physicochemical difference between arginine and cysteine. In-silico pathogenicity prediction programs like SIFT, Polyphen-2, MutationTaster2, CADD etc. predicted this variant to be likely disease causing as it may probably damage the protein structure and function. Varsome predicted this variant as VUS with minor pathogenic evidence but these predictions have not been confirmed by published functional studies and it's clinical significance is uncertain.

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

Last Updated: Oct 13, 2024

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