ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.353G>A (p.Arg118Lys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175608 SCV001339261 uncertain significance not specified 2020-03-03 criteria provided, single submitter clinical testing Variant summary: SPRED1 c.353G>A (p.Arg118Lys) results in a conservative amino acid change located in the WH1/EVH1 domain (IPR000697) and SPRE, EVH1 domain (IPR041937) 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 8e-06 in 250964 control chromosomes (gnomAD v2). Furthermore, the variant allele was found at a frequency of 0.00006983 in 143200 control chromosomes, predominantly at a frequency of 0.0002381 (10 individuals) within the African or African-American subpopulation in the gnomAD (v3) database. This variant frequency is approximately 95 fold of the estimated maximal expected allele frequency for a pathogenic variant in SPRED1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), suggesting the variant may be a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.353G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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