NM_004360.5(CDH1):c.764A>G (p.Gln255Arg) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002024824.8

Allele description [Variation Report for NM_004360.5(CDH1):c.764A>G (p.Gln255Arg)]

NM_004360.5(CDH1):c.764A>G (p.Gln255Arg)

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.764A>G (p.Gln255Arg)

HGVS:

NC_000016.10:g.68810273A>G
NG_008021.1:g.77982A>G
NM_001317184.2:c.764A>G
NM_001317185.2:c.-852A>G
NM_001317186.2:c.-1056A>G
NM_004360.4:c.764A>G
NM_004360.5:c.764A>GMANE SELECT
NP_001304113.1:p.Gln255Arg
NP_004351.1:p.Gln255Arg
LRG_301:g.77982A>G
NC_000016.9:g.68844176A>G

Protein change:

Q255R

Links:

dbSNP: rs2152131091

NCBI 1000 Genomes Browser:

rs2152131091

Molecular consequence:

NM_001317185.2:c.-852A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1056A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.764A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.764A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Clear Turn Off Turn On

Homo sapiens N-acylsphingosine amidohydrolase (acid ceramidase) 1, mRNA (cDNA cl...
Homo sapiens N-acylsphingosine amidohydrolase (acid ceramidase) 1, mRNA (cDNA clone MGC:9327 IMAGE:3923451), complete cds
gi|16741291|gb|BC016481.1|

Nucleotide

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
SCV002308337	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003926687	European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS	criteria provided, single submitter (Lee et al. (Hum Mutat. 2018))	Uncertain significance (Aug 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30311375, 36436516

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002308337

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2021)

germline

clinical testing

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

SCV003926687

European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS

criteria provided, single submitter

(Lee et al. (Hum Mutat. 2018))

Uncertain significance
(Aug 1, 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	no	not provided	2	not provided	not provided	not provided	clinical testing
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

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants.

Lee K, Krempely K, Roberts ME, Anderson MJ, Carneiro F, Chao E, Dixon K, Figueiredo J, Ghosh R, Huntsman D, Kaurah P, Kesserwan C, Landrith T, Li S, Mensenkamp AR, Oliveira C, Pardo C, Pesaran T, Richardson M, Slavin TP, Spurdle AB, Trapp M, et al.

Hum Mutat. 2018 Nov;39(11):1553-1568. doi: 10.1002/humu.23650.

PubMed [citation]

PMID:: 30311375
PMCID:: PMC6188664

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002308337.3

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

Description

This sequence change replaces glutamine with arginine at codon 255 of the CDH1 protein (p.Gln255Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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

From European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS, SCV003926687.1

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

Description

"2 families not fulfilling 2020 HDGC criteria-2 Familial history of breast cancer"

PubMed [ID: 36436516]

Description

PM2 (PMID: 30311375)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	2	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine