Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328225 | SCV001437599 | benign | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-10 | reviewed by expert panel | curation | The c.387+5G>A variant has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; SCV000329224.7, SCV000288482.5, SCV000186607.5). This variant was also observed in the homozygous state in an individual without a personal and/or family history of diffuse gastric cancer, lobular breast cancer (BP2_Strong; SCV000288482.5). RNA studies demonstrated no abnormal splicing (BS3; PMID: 31642931). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BS3, BP2_Strong. |
Ambry Genetics | RCV000131594 | SCV000186607 | likely benign | Hereditary cancer-predisposing syndrome | 2018-11-24 | 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 |
RCV000227422 | SCV000288482 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-01-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000315259 | SCV000329224 | likely benign | not provided | 2020-08-25 | criteria provided, single submitter | clinical testing | In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Published functional studies demonstrate no damaging effect: no aberrant splicing observed (Karam 2019); Identified in an individual with nonsyndromic cleft lip and palate (Brito 2015); This variant is associated with the following publications: (PMID: 31638429, 31642931, 30661051, 26123647) |
Counsyl | RCV000227422 | SCV000487845 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2015-11-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131594 | SCV000684457 | likely benign | Hereditary cancer-predisposing syndrome | 2021-07-26 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000227422 | SCV000839077 | benign | Hereditary diffuse gastric adenocarcinoma | 2023-08-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264448 | SCV001442610 | likely benign | not specified | 2020-10-05 | criteria provided, single submitter | clinical testing | Variant summary: CDH1 c.387+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 250142 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.387+5G>A has been reported in the literature in one individual affected with Nonsyndromic Cleft Lip with or without Cleft Palate (Brito_2015). This report does not provide unequivocal conclusions about association of the variant with Hereditary Diffuse Gastric Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likelye benign n=2, VUS n=4). Based on the evidence outlined above, the variant was classified as likely benign. |
Sema4, |
RCV000131594 | SCV002529178 | benign | Hereditary cancer-predisposing syndrome | 2021-08-17 | criteria provided, single submitter | curation | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000227422 | SCV003927033 | benign | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | BS2; BS3; BP2_Strong (PMID: 30311375) |
Myriad Genetics, |
RCV000227422 | SCV004020011 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-03-06 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000315259 | SCV004220830 | benign | not provided | 2023-05-11 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001264448 | SCV003839327 | likely benign | not specified | 2022-08-22 | no assertion criteria provided | clinical testing |