Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164075 | SCV000214685 | likely benign | Hereditary cancer-predisposing syndrome | 2020-09-14 | 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. |
Invitae | RCV003534437 | SCV000282826 | likely benign | Familial adenomatous polyposis 1 | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000226636 | SCV000488429 | uncertain significance | Familial adenomatous polyposis 1 | 2016-03-24 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000483633 | SCV000567924 | likely benign | not provided | 2019-11-05 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 27443514, 25479140, 29684080) |
Color Diagnostics, |
RCV000164075 | SCV000681878 | likely benign | Hereditary cancer-predisposing syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000483633 | SCV001470120 | likely benign | not provided | 2019-11-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001582644 | SCV001821417 | likely benign | not specified | 2023-12-11 | criteria provided, single submitter | clinical testing | Variant summary: APC c.7574G>A (p.Arg2525His) results in a non-conservative amino acid change located in the Adenomatous polyposis coli protein basic domain (IPR009234) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 250814 control chromosomes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is benign. c.7574G>A has been reported in the literature as a VUS in settings of multigene cancer panel testing in affected individuals with cancers such as endometrial, hereditary breast and/or ovarian cancers (example, Ring_2016, Schubert_2019, Okawa_2023). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36243179, 27443514, 30426508). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (likely benign, n=5; VUS, n=3). Based on the evidence outlined above, the variant was classified as likely benign. |
Sema4, |
RCV000164075 | SCV002528193 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-03 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV000226636 | SCV004017780 | likely benign | Familial adenomatous polyposis 1 | 2023-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. |
Prevention |
RCV003937504 | SCV004752575 | likely benign | APC-related condition | 2022-09-13 | criteria provided, single submitter | 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). |