NM_004360.5(CDH1):c.781G>T (p.Glu261Ter) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (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:: RCV000991090.11

Allele description [Variation Report for NM_004360.5(CDH1):c.781G>T (p.Glu261Ter)]

NM_004360.5(CDH1):c.781G>T (p.Glu261Ter)

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.781G>T (p.Glu261Ter)

HGVS:

NC_000016.10:g.68810290G>T
NG_008021.1:g.77999G>T
NM_001317184.2:c.781G>T
NM_001317185.2:c.-835G>T
NM_001317186.2:c.-1039G>T
NM_004360.4:c.781G>T
NM_004360.5:c.781G>TMANE SELECT
NP_001304113.1:p.Glu261Ter
NP_004351.1:p.Glu261Ter
LRG_301t1:c.781G>T
LRG_301:g.77999G>T
LRG_301p1:p.Glu261Ter
NC_000016.9:g.68844193G>T
NC_000016.9:g.68844193G>T
NM_004360.3:c.781G>T
NM_004360.4(CDH1):c.781G>T
p.Glu261Ter

Protein change:

E261*; GLU261TER

Links:

OMIM: 192090.0004; dbSNP: rs121964873

NCBI 1000 Genomes Browser:

rs121964873

Molecular consequence:

NM_001317185.2:c.-835G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1039G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.781G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004360.5:c.781G>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Homo sapiens hypothetical protein P15-2 (P15-2), mRNA
Homo sapiens hypothetical protein P15-2 (P15-2), mRNA
gi|8923951|ref|NM_018698.1|

Nucleotide
SYNJ1 [Malurus melanocephalus]
SYNJ1 [Malurus melanocephalus]
Gene ID:130585473

Gene
ASAH1 [Geospiza fortis]
ASAH1 [Geospiza fortis]
Gene ID:102045042

Gene
RPL10A ribosomal protein L10a [Canis lupus familiaris]
RPL10A ribosomal protein L10a [Canis lupus familiaris]
Gene ID:474884

Gene
Same Parent, Connectivity for PubChem Compound (Select 136050659) (2)
PubChem Compound

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002147714	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 11, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15235021, 20373070, 9744472, 28492532
SCV003926688	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))	Pathogenic (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

SCV002147714

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 11, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003926688

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))

Pathogenic
(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	yes	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

Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.

Brooks-Wilson AR, Kaurah P, Suriano G, Leach S, Senz J, Grehan N, Butterfield YS, Jeyes J, Schinas J, Bacani J, Kelsey M, Ferreira P, MacGillivray B, MacLeod P, Micek M, Ford J, Foulkes W, Australie K, Greenberg C, LaPointe M, Gilpin C, Nikkel S, et al.

J Med Genet. 2004 Jul;41(7):508-17.

PubMed [citation]

PMID:: 15235021
PMCID:: PMC1735838

Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice.

Guilford P, Humar B, Blair V.

Gastric Cancer. 2010 Mar;13(1):1-10. doi: 10.1007/s10120-009-0531-x. Epub 2010 Apr 7. Review.

PubMed [citation]

PMID:: 20373070

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002147714.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu261*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with lobular breast cancer (PMID: 9744472). ClinVar contains an entry for this variant (Variation ID: 12234).

#	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, SCV003926688.1

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

Description

"2 families fulfilling 2020 HDGC criteria-2 Familial history of gastric cancer"

PubMed [ID: 36436516]

Description

PVS1; PS4_Moderate; PM2 (PMID: 30311375)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	2	not provided

Last Updated: Sep 29, 2024

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