Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041240 | SCV000064931 | benign | not specified | 2018-05-25 | criteria provided, single submitter | clinical testing | p.Asp9Val in exon 1 of SPRED1: This variant is classified as benign because it h as been identified in 0.5% (49/9150) of Ashkenazi Jewish chromosomes by the Geno me Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs20015 7475). ACMG/AMP criteria applied: BA1. |
Gene |
RCV000680360 | SCV000530149 | likely benign | not provided | 2019-10-11 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26635368, 22753041, 31401120) |
Invitae | RCV001082112 | SCV000645821 | benign | Legius syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000680360 | SCV001149385 | likely benign | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | SPRED1: BS1 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000041240 | SCV001338222 | benign | not specified | 2020-02-24 | criteria provided, single submitter | clinical testing | Variant summary: SPRED1 c.26A>T (p.Asp9Val) results in a non-conservative amino acid change located in the WH1/EVH1 domain (IPR000697) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00068 in 195612 control chromosomes, predominantly at a frequency of 0.0025 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1000 fold of the estimated maximal expected allele frequency for a pathogenic variant in SPRED1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been internally reported (PTPN11 c.172A>T, p.Asn58Tyr), providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cites the variant as uncertain significance (1x), likely benign (1x) and benign (2x). Based on the evidence outlined above, the variant was classified as benign. |
Genome Diagnostics Laboratory, |
RCV001813368 | SCV002060693 | benign | Noonan syndrome and Noonan-related syndrome | 2019-10-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002453336 | SCV002739949 | benign | Cardiovascular phenotype | 2021-11-01 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: 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. |
Prevention |
RCV003944953 | SCV004770781 | likely benign | SPRED1-related condition | 2022-05-16 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |