Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000205771 | SCV000259293 | likely benign | Fanconi anemia | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001310662 | SCV000278974 | likely benign | not provided | 2020-10-13 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24728327, 21279724, 28767289) |
Ambry Genetics | RCV001011455 | SCV001171777 | benign | Hereditary cancer-predisposing syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Ce |
RCV001310662 | SCV001500549 | likely benign | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001509574 | SCV001716360 | likely benign | Fanconi anemia complementation group C | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000205771 | SCV002535090 | uncertain significance | Fanconi anemia | 2021-08-05 | criteria provided, single submitter | curation | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000120972 | SCV004122043 | likely benign | not specified | 2023-10-24 | criteria provided, single submitter | clinical testing | Variant summary: FANCC c.1414G>A (p.Gly472Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 251292 control chromosomes, predominantly at a frequency of 0.0025 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCC causing Fanconi Anemia Group C phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.1414G>A has been reported in the literature in individuals affected with Pancreas cancer (example, Bhai_2021, Shindo_2017), without strong evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Fanconi Anemia Group C or other FANCC related diseases. 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: 34326862, 28767289). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (Likely benign, n=4, Benign, n=1, VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001310662 | SCV004218668 | likely benign | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000120972 | SCV000085140 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |