Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000163107 | SCV000213616 | likely benign | Hereditary cancer-predisposing syndrome | 2014-12-22 | 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 |
RCV001085146 | SCV000254828 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-01-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000437397 | SCV000515549 | likely benign | not specified | 2018-01-25 | 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, |
RCV000163107 | SCV000684448 | likely benign | Hereditary cancer-predisposing syndrome | 2016-05-24 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588174 | SCV000698392 | benign | not provided | 2017-02-02 | criteria provided, single submitter | clinical testing | Variant summary: The CDH1 c.2637C>T (p.Gly879Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change in the last exon (10bp upstream of the stop codon). One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. 5/5 splice prediction tools predict a gain of a cryptic splicing donor site. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 6/121264 control chromosomes at a frequency of 0.0000495, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283), suggesting this variant is likely a benign polymorphism. This variant was reported in Wilms' tumor sample without germline status confirmed. One internal sample also carried a pathogenic variant in BRIP1 c.3651G>A/p.W1217*, futher supporting the benign nature of this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798568 | SCV002043277 | likely benign | Breast and/or ovarian cancer | 2023-04-25 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000163107 | SCV002529162 | benign | Hereditary cancer-predisposing syndrome | 2021-03-04 | criteria provided, single submitter | curation | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV001085146 | SCV003926973 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | BS2_Supporting; BP7 (PMID: 30311375) |
Ce |
RCV000588174 | SCV004140038 | likely benign | not provided | 2024-11-01 | criteria provided, single submitter | clinical testing | CDH1: BP4, BP7 |
Myriad Genetics, |
RCV001085146 | SCV005405159 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-09-24 | 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, |
RCV000588174 | SCV001552217 | likely benign | not provided | no assertion criteria provided | clinical testing | The CDH1 p.Gly879= variant was identified in 1 of 270 proband chromosomes (frequency: 0.004) from individuals or families with carcinomas of the endometrium and ovary (Risinger 1994). The variant was also identified in the following databases: dbSNP (ID: rs141001592) as "With Likely benign allele", ClinVar (3x likely benign, 2x benign), Clinvitae, and the Zhejiang Colon Cancer Database (1x). The variant was not identified in Cosmic, MutDB, or the Insight Colon Cancer Gene Variant Database. The variant was identified in control databases in 15 of 246200 chromosomes at a frequency of 0.00006 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 4 of 15304 chromosomes (freq: 0.0003), European in 7 of 111662 chromosomes (freq: 0.00006), East Asian in 2 of 17248 chromosomes (freq: 0.0001), and South Asian in 2 of 30782 chromosomes (freq: 0.00007). The variant was not observed in the Other, Latino, Ashkenazi Jewish, or Finnish populations. Multiple studies have listed this variant as a polymorphism (Berx 1998, Risinger 1994). The p.Gly879= 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. However, 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% 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. |