ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.48+5C>T

dbSNP: rs77312180
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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 RCV003328433 SCV001142237 likely benign CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-18 reviewed by expert panel curation The c.48+5C>T variant was observed in at least 3 families without a personal and/or family history of diffuse gastric cancer, lobular breast cancer or a signet ring cell tumor (BP2_Supporting; internal data). There are at least 3 in silico predictors in agreement that this variant does not affect splicing (BP4). Therefore, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2_Supporting, BP4.
Color Diagnostics, LLC DBA Color Health RCV000584292 SCV000689545 likely benign Hereditary cancer-predisposing syndrome 2016-10-07 criteria provided, single submitter clinical testing
GeneDx RCV000603540 SCV000728923 likely benign not specified 2017-04-19 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.
Invitae RCV000639243 SCV000760813 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-11-07 criteria provided, single submitter clinical testing This variant is present in population databases (rs77312180, gnomAD 0.009%). This sequence change falls in intron 1 of the CDH1 gene. It does not directly change the encoded amino acid sequence of the CDH1 protein. It affects a nucleotide within the consensus splice site. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 491543).
Ambry Genetics RCV000584292 SCV002639574 likely benign Hereditary cancer-predisposing syndrome 2021-11-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.

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