NM_004360.5(CDH1):c.1587dup (p.Ala530fs) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 22, 2023
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:: RCV001260575.7

Allele description [Variation Report for NM_004360.5(CDH1):c.1587dup (p.Ala530fs)]

NM_004360.5(CDH1):c.1587dup (p.Ala530fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.1587dup (p.Ala530fs)

HGVS:

NC_000016.10:g.68819301dup
NG_008021.1:g.87010dup
NM_001317184.2:c.1404dup
NM_001317185.2:c.39dup
NM_001317186.2:c.-254-2700dup
NM_004360.5:c.1587dupMANE SELECT
NP_001304113.1:p.Ala469fs
NP_001304114.1:p.Ala14fs
NP_004351.1:p.Ala530fs
LRG_301t1:c.1587dup
LRG_301:g.87010dup
NC_000016.9:g.68853203_68853204insT
NC_000016.9:g.68853204dup
NM_004360.3:c.1587dupT
NM_004360.4:c.1587dup
NM_004360.5(CDH1):c.1587dupMANE SELECT
p.Ala530fs

Protein change:

A14fs

Links:

dbSNP: rs1555516532

NCBI 1000 Genomes Browser:

rs1555516532

Molecular consequence:

NM_001317184.2:c.1404dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317185.2:c.39dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.1587dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317186.2:c.-254-2700dup - 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

Recent activity

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rhodopsin, partial [Apterichtus klazingai]
rhodopsin, partial [Apterichtus klazingai]
gi|1517359724|gb|AYW11981.1|

Protein
THI12 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase [Saccharomyc...
THI12 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase [Saccharomyces cerevisiae S288C]
Gene ID:855384

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002243027	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15235021, 20373070, 28492532
SCV004044095	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jun 14, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002243027

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004044095

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Jun 14, 2023)

unknown

clinical testing

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
not provided	unknown	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, SCV002243027.3

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

Description

This sequence change creates a premature translational stop signal (p.Ala530Cysfs*7) 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 (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 422539). For these reasons, this variant has been classified as Pathogenic.

#	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 Myriad Genetics, Inc., SCV004044095.2

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

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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

Last Updated: Sep 29, 2024

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