Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000522135 | SCV000616485 | benign | RASopathy | 2017-04-18 | reviewed by expert panel | curation | The filtering allele frequency of the c.1141G>A (p.Asp381Asn) variant in the RAF1 gene is 0.162% (36/16508) of South Asian 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) |
Gene |
RCV000159079 | SCV000209022 | benign | not specified | 2017-02-07 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000159079 | SCV001361782 | benign | not specified | 2019-07-15 | criteria provided, single submitter | clinical testing | Variant summary: RAF1 c.1141G>A (p.Asp381Asn) results in a conservative amino acid change located in the Serine-threonine/tyrosine-protein kinase, catalytic domain (IPR001245) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 251374 control chromosomes, predominantly at a frequency of 0.0023 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 90 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 South Asian origin. c.1141G>A has been reported in the literature in an individual with suspected RASopathy, presenting with "congenital hypoplasia of the lung, congenital anomaly of ribs and sternum, polyhydramnios, hydrops fetalis, died on DOL 12," however, authors classified the variant as likely benign (Bhoj_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) from an expert panel (ClinGen) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Labcorp Genetics |
RCV000522135 | SCV001598755 | likely benign | RASopathy | 2024-01-17 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001813412 | SCV002060599 | benign | Noonan syndrome and Noonan-related syndrome | 2020-12-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002453552 | SCV002615403 | benign | Cardiovascular phenotype | 2021-02-15 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Service de Génétique Moléculaire, |
RCV001261134 | SCV001438541 | uncertain significance | Noonan syndrome with multiple lentigines; Noonan syndrome | no assertion criteria provided | clinical testing |