NM_004360.5(CDH1):c.1711+5G>A AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 20, 2021
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:: RCV001856947.8

Allele description [Variation Report for NM_004360.5(CDH1):c.1711+5G>A]

NM_004360.5(CDH1):c.1711+5G>A

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.1711+5G>A

HGVS:

NC_000016.10:g.68819430G>A
NG_008021.1:g.87139G>A
NM_001317184.2:c.1528+5G>A
NM_001317185.2:c.163+5G>A
NM_001317186.2:c.-254-2571G>A
NM_004360.5:c.1711+5G>AMANE SELECT
LRG_301t1:c.1711+5G>A
LRG_301:g.87139G>A
NC_000016.9:g.68853333G>A
NM_004360.3:c.1711+5G>A

Links:

dbSNP: rs1131690818

NCBI 1000 Genomes Browser:

rs1131690818

Molecular consequence:

NM_001317184.2:c.1528+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317185.2:c.163+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317186.2:c.-254-2571G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_004360.5:c.1711+5G>A - 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
SCV002274869	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 20, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17576681, 9536098, 15235021, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002274869

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 20, 2021)

germline

clinical testing

PubMed (4)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002274869.3

#	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 falls in intron 11 of the CDH1 gene. It does not directly change the encoded amino acid sequence of the CDH1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with skipping of exon 11, which introduces a premature termination codon (PMID: 15235021). The resulting mRNA is expected to undergo nonsense-mediated decay. This variant has been observed in individual(s) with hereditary diffuse gastric cancer syndrome (PMID: 15235021, Invitae). ClinVar contains an entry for this variant (Variation ID: 428630). This variant is not present in population databases (ExAC no frequency).

#	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: Oct 20, 2024

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