Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264442 | SCV001442599 | benign | not specified | 2020-10-01 | criteria provided, single submitter | clinical testing | Variant summary: SPRED1 c.32+20C>T 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 0.00026 in 174256 control chromosomes, predominantly at a frequency of 0.00076 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 135 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 a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.32+20C>T in individuals affected with Neurofibromatosis Type 1-Like Syndrome (Legius Syndrome) 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 benign. |
| Invitae | RCV001760309 | SCV002468870 | benign | Legius syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing |