Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164509 | SCV000215160 | likely benign | Hereditary cancer-predisposing syndrome | 2019-06-19 | 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. |
Counsyl | RCV000409101 | SCV000487966 | uncertain significance | Familial adenomatous polyposis 1 | 2015-12-22 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000432869 | SCV000531163 | likely benign | not specified | 2017-09-01 | 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 | RCV000409101 | SCV000552752 | likely benign | Familial adenomatous polyposis 1 | 2022-11-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000164509 | SCV000911385 | benign | Hereditary cancer-predisposing syndrome | 2017-04-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000432869 | SCV001748700 | likely benign | not specified | 2021-07-04 | criteria provided, single submitter | clinical testing | Variant summary: APC c.835-3T>C 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 2e-05 in 250968 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.835-3T>C has been reported in the literature as a VUS in settings of multigene panel testing in individuals affected with colorectal cancer (example, Yurgelun_2017). 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. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation with a majority consensus leaning towards benign (n=1)/likely benign(n=3). Based on the evidence outlined above, the variant was classified as likely benign. |
Genetic Services Laboratory, |
RCV000432869 | SCV002071997 | uncertain significance | not specified | 2021-11-19 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the APC gene demonstrated a sequence change in intron 8, c.835-3T>C. This sequence change has been described in the gnomAD database with a frequency of 0.004% in the non-Finnish European subpopulation (dbSNP rs372090940). This sequence change is not predicted to have a deleterious effect on splicing based on in-silico splice prediction programs. This sequence change has been previously described in an individual with colorectal cancer (PMID: 28135145). It is possible that this sequence change represents a benign sequence change in the APC gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined. |
Myriad Genetics, |
RCV000409101 | SCV004017758 | likely benign | Familial adenomatous polyposis 1 | 2023-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. |
Genome Diagnostics Laboratory, |
RCV001729422 | SCV001977774 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001729422 | SCV001977994 | likely benign | not provided | no assertion criteria provided | clinical testing |