NM_004360.5(CDH1):c.76G>A (p.Glu26Lys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 19, 2024
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:: RCV001026730.4

Allele description [Variation Report for NM_004360.5(CDH1):c.76G>A (p.Glu26Lys)]

NM_004360.5(CDH1):c.76G>A (p.Glu26Lys)

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.76G>A (p.Glu26Lys)

HGVS:

NC_000016.10:g.68738324G>A
NG_008021.1:g.6033G>A
NM_001317184.2:c.76G>A
NM_001317185.2:c.-1540G>A
NM_001317186.2:c.-1744G>A
NM_004360.5:c.76G>AMANE SELECT
NP_001304113.1:p.Glu26Lys
NP_004351.1:p.Glu26Lys
LRG_301t1:c.76G>A
LRG_301:g.6033G>A
NC_000016.9:g.68772227G>A
NM_004360.3:c.76G>A

Protein change:

E26K

Links:

dbSNP: rs786201058

NCBI 1000 Genomes Browser:

rs786201058

Molecular consequence:

NM_001317185.2:c.-1540G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1744G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001189167	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 19, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001189167

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 19, 2024)

germline

clinical testing

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

Citation Link

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

CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer.

Pan Z, Fu Z, Luo C, Bao Y, Wang M, Cao W, Xu X.

J Cancer Res Clin Oncol. 2022 Aug;148(8):2145-2151. doi: 10.1007/s00432-021-03775-4. Epub 2021 Sep 18.

PubMed [citation]

PMID:: 34537906

Details of each submission

From Ambry Genetics, SCV001189167.5

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

Description

The p.E26K variant (also known as c.76G>A), located in coding exon 2 of the CDH1 gene, results from a G to A substitution at nucleotide position 76. The glutamic acid at codon 26 is replaced by lysine, an amino acid with similar properties. This variant was identified in an Chinese individual meeting clinical criteria for hereditary diffuse gastric cancer (HDGC) but was classified as benign by authors based on in silico analyses (Pan Z et al. J Cancer Res Clin Oncol, 2022 Aug;148:2145-2151). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

#	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

ClinVar

Relating variation to medicine