Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000520321 | SCV000616484 | benign | RASopathy | 2017-04-18 | reviewed by expert panel | curation | The filtering allele frequency of the c.1587G>A (p.Ser529=) variant in the RAF1 gene is 0.052% (10/10402) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193137 | SCV001361780 | benign | not specified | 2019-05-06 | criteria provided, single submitter | clinical testing | Variant summary: RAF1 c.1587G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 7.6e-05 in 251432 control chromosomes, predominantly at a frequency of 0.00086 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 34 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAF1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1587G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters including one expert panel have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Labcorp Genetics |
RCV000520321 | SCV001729461 | benign | RASopathy | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000859502 | SCV001909482 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002399356 | SCV002705222 | likely benign | Cardiovascular phenotype | 2018-12-24 | 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. |