ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.207+15A>G

gnomAD frequency: 0.00073  dbSNP: rs377288061
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436128 SCV000527116 likely benign not provided 2021-02-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001527027 SCV001737849 benign not specified 2021-05-24 criteria provided, single submitter clinical testing Variant summary: SPRED1 c.207+15A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 249582 control chromosomes. The observed variant frequency is approximately 22 fold of the estimated maximal expected allele frequency for a pathogenic variant in SPRED1 causing Neurofibromatosis Type 1-Like Syndrome (Legius Syndrome) phenotype (5.6e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.207+15A>G in individuals affected with Neurofibromatosis Type 1-Like Syndrome (Legius Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. At-least one co-occurrence with another pathogenic variant has been observed at our laboratory (PTPN11 c.188A>G , p.Tyr63Cys), providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV002059586 SCV002445880 benign Legius syndrome 2024-01-31 criteria provided, single submitter clinical testing

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