NM_004360.5(CDH1):c.360dup (p.His121fs) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 8, 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:: RCV000227876.7

Allele description [Variation Report for NM_004360.5(CDH1):c.360dup (p.His121fs)]

NM_004360.5(CDH1):c.360dup (p.His121fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.360dup (p.His121fs)

Other names:

NM_004360.5(CDH1):c.360dup; p.His121fs

HGVS:

NC_000016.10:g.68801866dup
NG_008021.1:g.69575dup
NM_001317184.2:c.360dup
NM_001317185.2:c.-1256dup
NM_001317186.2:c.-1460dup
NM_004360.5:c.360dupMANE SELECT
NP_001304113.1:p.His121fs
NP_004351.1:p.His121fs
LRG_301t1:c.360dup
LRG_301:g.69575dup
NC_000016.9:g.68835765_68835766insG
NC_000016.9:g.68835769dup
NM_004360.3:c.360dupG
NM_004360.4:c.360dup

Protein change:

H121fs

Links:

dbSNP: rs878854690

NCBI 1000 Genomes Browser:

rs878854690

Molecular consequence:

NM_001317185.2:c.-1256dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1460dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.360dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.360dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000288479	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15235021, 20373070, 28492532
SCV004044612	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jun 8, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000288479

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2020)

germline

clinical testing

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

SCV004044612

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Jun 8, 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 Invitae, SCV000288479.5

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 239903). This sequence change creates a premature translational stop signal (p.His121Alafs*47) in the CDH1 gene. It is expected to result in an absent or disrupted protein product.

#	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., SCV004044612.2

#	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: Feb 14, 2024

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