ClinVar Miner

Submissions for variant NM_001354689.3(RAF1):c.1689G>C (p.Thr563=) (rs5746244)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000459831 SCV000616483 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.1629G>C (p.Thr543=) variant in the RAF1 gene is 0.054% (9/8654) of East 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)
Invitae RCV000459831 SCV000562253 likely benign Rasopathy 2020-11-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000157703 SCV000698122 benign not provided 2016-06-27 criteria provided, single submitter clinical testing Variant summary: The RAF1 c.1629G>C (p.Thr543Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant, but 5/5 splicing algorithms predict no significant change to splicing. This variant was found in 11/121396 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.00104 (9/8654). This subpopulation frequency is about 42 times the estimated maximal expected allele frequency of a pathogenic RAF1 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant has been observed in one Japanese Kabuki Syndrome patient (Kuniba_ AJMG_2008) and one South Indian individual phenotype not specified (Dhandapany_Nat Genet_2015); data was not provided to suggest a causal relationship with the variant of interest. Additionally, one clinical diagnostic laboratory classified this variant as a VUS without providing evidence to independently evaluate. Taken together, this variant is classified as Benign based on the nature of the variant and the high allele frequency in the East Asian ExAC subpopulation.
Illumina Clinical Services Laboratory,Illumina RCV001146462 SCV001307208 benign LEOPARD syndrome 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001148647 SCV001309553 likely benign Noonan syndrome 5 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Greenwood Genetic Center Diagnostic Laboratories,Greenwood Genetic Center RCV000157703 SCV000207691 uncertain significance not provided 2015-01-15 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.