NM_004360.5(CDH1):c.1711+1G>A AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Dec 11, 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:: RCV000690117.10

Allele description [Variation Report for NM_004360.5(CDH1):c.1711+1G>A]

NM_004360.5(CDH1):c.1711+1G>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+1G>A

HGVS:

NC_000016.10:g.68819426G>A
NG_008021.1:g.87135G>A
NM_001317184.2:c.1528+1G>A
NM_001317185.2:c.163+1G>A
NM_001317186.2:c.-254-2575G>A
NM_004360.4:c.1711+1G>A
NM_004360.5:c.1711+1G>AMANE SELECT
LRG_301t1:c.1711+1G>A
LRG_301:g.87135G>A
NC_000016.9:g.68853329G>A
NC_000016.9:g.68853329G>A
NM_004360.3:c.1711+1G>A
NM_004360.4(CDH1):c.1711+1G>A

Links:

dbSNP: rs886041161

NCBI 1000 Genomes Browser:

rs886041161

Molecular consequence:

NM_001317186.2:c.-254-2575G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317184.2:c.1528+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001317185.2:c.163+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004360.5:c.1711+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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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Homo sapiens NLR family apoptosis inhibitory protein (NAIP), RefSeqGene on chrom...
Homo sapiens NLR family apoptosis inhibitory protein (NAIP), RefSeqGene on chromosome 5
gi|209447065|ref|NG_008724.1|

Nucleotide
RecName: Full=UDP-glucuronosyltransferase 1A1; Short=UGT1A1; AltName: Full=B1; A...
RecName: Full=UDP-glucuronosyltransferase 1A1; Short=UGT1A1; AltName: Full=B1; AltName: Full=UDP-glucuronosyltransferase 1-1; Short=UDPGT 1-1; Short=UGT1*1; Short=UGT1-01; Short=UGT1.1; Flags: Precursor
gi|2501473|sp|Q64550.1|UD11_RAT

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000817795	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004044207	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Jun 14, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000817795

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 11, 2023)

germline

clinical testing

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

SCV004044207

Myriad Genetics, Inc.

criteria provided, single submitter

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

Likely 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000817795.5

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

Description

This sequence change affects a donor splice site in intron 11 of the CDH1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. 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: 428628). Studies have shown that disruption of this splice site results in skipping of exon 11 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.

#	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., SCV004044207.2

#	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 likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

#	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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