NM_004360.5(CDH1):c.377dup (p.Pro127fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 9, 2020
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:: RCV002256660.4

Allele description [Variation Report for NM_004360.5(CDH1):c.377dup (p.Pro127fs)]

NM_004360.5(CDH1):c.377dup (p.Pro127fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.377dup (p.Pro127fs)

HGVS:

NC_000016.10:g.68801883dup
NG_008021.1:g.69592dup
NM_001317184.2:c.377dup
NM_001317185.2:c.-1239dup
NM_001317186.2:c.-1443dup
NM_004360.5:c.377dupMANE SELECT
NP_001304113.1:p.Pro127fs
NP_004351.1:p.Pro127fs
LRG_301t1:c.377dup
LRG_301:g.69592dup
NC_000016.9:g.68835780_68835781insC
NC_000016.9:g.68835786dup
NM_004360.3:c.377dup
NM_004360.3:c.377dupC

Protein change:

P127fs

Links:

dbSNP: rs1060501215

NCBI 1000 Genomes Browser:

rs1060501215

Molecular consequence:

NM_001317185.2:c.-1239dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1443dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.377dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.377dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002529176	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely pathogenic (Dec 9, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002625761	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 8, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002529176

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely pathogenic
(Dec 9, 2020)

germline

curation

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

Citation Link,

SCV002625761

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 8, 2020)

germline

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, curation

Citations

PubMed

Gene mutations distinguishing gastric from colorectal and esophageal adenocarcinomas.

Hoang T, Ganesan AK, Hiyama D, Dayyani F.

J Gastrointest Oncol. 2020 Feb;11(1):45-54. doi: 10.21037/jgo.2019.12.06.

PubMed [citation]

PMID:: 32175104
PMCID:: PMC7052769

Details of each submission

From Sema4, Sema4, SCV002529176.1

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

#	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 Ambry Genetics, SCV002625761.2

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

Description

The c.377dupC pathogenic mutation, located in coding exon 3 of the CDH1 gene, results from a duplication of C at nucleotide position 377, causing a translational frameshift with a predicted alternate stop codon (p.P127Afs*41). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 7, 2024

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