ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.164-4G>A

dbSNP: rs780375749
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328254 SCV004035121 likely benign CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-02 reviewed by expert panel curation The c.164-4G>A (NM_004360.5) variant in CDH1 occurs in the splice donor region of intron 2. This variant has been observed in more than 10 individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; Ambry, GeneDx, Invitae). This variant occurs in one in 251,376 alleles in gnomAD 2.1.1 (less than one out of 100,000), within the European Non-Finnish population (one in 113,662 alleles) PM2_Supporting. In silico splice site predictors suggest that this variant does not impact splicing (BP4). However, splicing has not been assessed by in vitro assays. In summary, this variant meets the criteria to be classified as likely benign for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PM2_Supporting, BS2, BP4. (CDH1 VCEP specifications version 3.1; 04/24/2023)
Ambry Genetics RCV000165020 SCV000215717 likely benign Hereditary cancer-predisposing syndrome 2024-09-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000548980 SCV000637740 likely benign Hereditary diffuse gastric adenocarcinoma 2023-05-13 criteria provided, single submitter clinical testing
GeneDx RCV000608093 SCV000726457 likely benign not specified 2018-01-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Myriad Genetics, Inc. RCV000548980 SCV005405849 likely benign Hereditary diffuse gastric adenocarcinoma 2024-09-12 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.

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