NM_004360.5(CDH1):c.1695_1696insTT (p.Ile566fs) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 18, 2020
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:: RCV001387465.5

Allele description [Variation Report for NM_004360.5(CDH1):c.1695_1696insTT (p.Ile566fs)]

NM_004360.5(CDH1):c.1695_1696insTT (p.Ile566fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.1695_1696insTT (p.Ile566fs)

HGVS:

NC_000016.10:g.68819409_68819410insTT
NG_008021.1:g.87118_87119insTT
NM_001317184.2:c.1512_1513insTT
NM_001317185.2:c.147_148insTT
NM_001317186.2:c.-254-2592_-254-2591insTT
NM_004360.5:c.1695_1696insTTMANE SELECT
NP_001304113.1:p.Ile505fs
NP_001304114.1:p.Ile50fs
NP_004351.1:p.Ile566fs
LRG_301:g.87118_87119insTT
NC_000016.9:g.68853312_68853313insTT

Protein change:

I505fs

Links:

dbSNP: rs2152137001

NCBI 1000 Genomes Browser:

rs2152137001

Molecular consequence:

NM_001317184.2:c.1512_1513insTT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317185.2:c.147_148insTT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.1695_1696insTT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317186.2:c.-254-2592_-254-2591insTT - intron variant - [Sequence Ontology: SO:0001627]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001588083	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 18, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15235021, 20373070, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001588083

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 18, 2020)

germline

clinical testing

PubMed (3)
[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	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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001588083.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. 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 creates a premature translational stop signal (p.Ile566Leufs*2) 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).

#	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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