Submissions for variant NM_002880.4(RAF1):c.-204G>C

dbSNP: rs547543588

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV001030083	SCV001192875	benign	RASopathy	2019-11-04	reviewed by expert panel	curation	The c.-204G>C variant in RAF1 is classified as benign because it has been identified in 0.15126% (95% CI of 32/15402) of non-Finnish European chromosomes in gnomAD (BA1; https://gnomad.broadinstitute.org). This variant is not located within the splice consensus sequence and computational splice site prediction tools do not predict an impact on splicing (BP4, BP7). ACMG/AMP Criteria applied: BA1, BP4, BP7.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154474	SCV000204143	likely benign	not specified	2011-03-25	criteria provided, single submitter	clinical testing	-204G>C in the 5'UTR of RAF1: This variant has been identified in our laboratory in four probands with clinical features of Noonan spectrum disorders. However, this variant was also identified in a parent of three of these individuals who r eportedly do not have clinical features associated with Noonan spectrum disorder s. Furthermore, this variant is located in the 5'UTR and although variants in re gulatory regions could have an effect on transcriptional or translational effici ency, variants of this type have not been reported in Noonan spectrum disorders to date. Therefore, this variant is likely to be benign.
Illumina Laboratory Services, Illumina	RCV000331154	SCV000440651	uncertain significance	Noonan syndrome 5	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000383491	SCV000440652	uncertain significance	LEOPARD syndrome 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001636611	SCV001850708	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001636611	SCV002585960	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	RAF1: BS1
Fulgent Genetics, Fulgent Genetics	RCV002490450	SCV002805394	likely benign	LEOPARD syndrome 2; Noonan syndrome 5; Dilated cardiomyopathy 1NN	2021-11-11	criteria provided, single submitter	clinical testing