Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001084921 | SCV000645825 | benign | Legius syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588911 | SCV000699961 | benign | not provided | 2017-04-17 | criteria provided, single submitter | clinical testing | Variant summary: The SPRED1 c.446G>A (p.Ser149Asn) variant involves the alteration of a conserved nucleotide. The variant lies within the WH1/EVH1 domain and the PH domain-like domain (InterPro). 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in the large control database ExAC in 113/123230 control chromosomes of all ethnicities, but was predominantly observed in the South Asian subpopulation at a frequency of 0.006663 (110/16510 with 3 homozygotes). This frequency is about 2665 times the estimated maximal expected allele frequency of a pathogenic SPRED1 variant (0.0000025), providing strong evidence that this is likely a benign polymorphism found primarily in the populations of South Asian origin. Two studies identified the variant in patient cohorts, one of which identified an unaffected father of the proband carrying the variant, showing lack of cosegregation (Messiaen_JAMA_2009). Additionally, functional studies that measured inhibition of MEK, ERK activation, FGF-induced Elk1 activation, Raf1 kinase activity and phosphorylation, and effect this variant on differentiation of PC12 cells show that this variant behaves similar to the WT control, in contrary to several truncating mutations also tested, suggesting the variant has no significant functional effect (Brems_Nat Genet_2007, Messiaen_JAMA_2009). Taken together, this variant is classified as benign. |
| Gene |
RCV000602111 | SCV000730357 | benign | not specified | 2018-02-01 | 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. |
| Genetic Services Laboratory, |
RCV000602111 | SCV002071770 | benign | not specified | 2021-08-03 | criteria provided, single submitter | clinical testing | |
| KCCC/NGS Laboratory, |
RCV001084921 | SCV004015553 | benign | Legius syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing |