Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000162667 | SCV000213114 | likely benign | Hereditary cancer-predisposing syndrome | 2014-08-21 | 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 |
RCV001083994 | SCV000253429 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000417807 | SCV000512514 | benign | not specified | 2015-09-04 | 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. |
Color Diagnostics, |
RCV000162667 | SCV000689572 | likely benign | Hereditary cancer-predisposing syndrome | 2017-05-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589062 | SCV000698413 | benign | not provided | 2016-11-04 | criteria provided, single submitter | clinical testing | Variant summary: The CDH1 c.894C>T (p.Ala298Ala) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts that this variant may affect ESE binding, however, these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 22/121408 (1/5518), which exceeds the estimated maximal expected allele frequency for a pathogenic CDH1 variant of 1/35335, suggesting this variant is likely a benign polymorphism. The variant of interest has been reported in an affected individual, however, with limited information (ie, lack of co-occurrence and cosegregation data) and the authors classify the variant as a "polymorphism." In addition, multiple clinical diagnostic laboratories cite the variant as "likely benign." Therefore, the variant of interest has been classified as Benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589062 | SCV000888045 | benign | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001083994 | SCV001274413 | benign | Hereditary diffuse gastric adenocarcinoma | 2018-03-06 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Sema4, |
RCV000162667 | SCV002529222 | benign | Hereditary cancer-predisposing syndrome | 2021-09-04 | criteria provided, single submitter | curation | |
CHEO Genetics Diagnostic Laboratory, |
RCV003149990 | SCV003837768 | likely benign | Breast and/or ovarian cancer | 2022-12-14 | criteria provided, single submitter | clinical testing | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV001083994 | SCV003926701 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | BP4; BP7 (PMID: 30311375) |
Myriad Genetics, |
RCV001083994 | SCV005405319 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-09-16 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Department of Pathology and Laboratory Medicine, |
RCV001357570 | SCV001553076 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The CDH1 p.Ala298= variant was identified in 1 of 472 proband chromosomes (frequency: 0.002) from individuals or families with gastric cancer and was not identified in 480 control chromosomes from healthy individuals (Chen 2013). The variant was also identified in dbSNP (ID: rs139110184) as "With Likely benign allele", ClinVar (classified as benign by GeneDx and one other clinical laboratory; classified as likely benign by Ambry Genetics, Invitae, and Color Genomics). The variant was not identified in Cosmic or Zhejiang University Database. The variant was identified in control databases in 39 of 277202 chromosomes at a frequency of 0.00014 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24032 chromosomes (freq: 0.00004), European in 27 of 126700 chromosomes (freq: 0.0002), East Asian in 2 of 18868 chromosomes (freq: 0.0001), Finnish in 9 of 25788 chromosomes (freq: 0.0003), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, or South Asian populations. The p.Ala298= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. | |
Institute for Biomarker Research, |
RCV000162667 | SCV001950160 | likely benign | Hereditary cancer-predisposing syndrome | 2021-09-15 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003937481 | SCV004749711 | likely benign | CDH1-related disorder | 2019-05-22 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |