Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000291489 | SCV000427818 | uncertain significance | 3M syndrome 2 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000934149 | SCV001079866 | likely benign | not provided | 2023-07-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002521397 | SCV003732721 | uncertain significance | Inborn genetic diseases | 2022-01-04 | criteria provided, single submitter | clinical testing | The c.2887G>A (p.E963K) alteration is located in exon 8 (coding exon 8) of the OBSL1 gene. This alteration results from a G to A substitution at nucleotide position 2887, causing the glutamic acid (E) at amino acid position 963 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003401355 | SCV004122765 | likely benign | not specified | 2023-10-11 | criteria provided, single submitter | clinical testing | Variant summary: OBSL1 c.2887G>A (p.Glu963Lys) results in a conservative amino acid change located in the Immunoglobulin subtype 2 domain (IPR003598) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00026 in 280568 control chromosomes, predominantly at a frequency of 0.0053 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately five fold of the estimated maximal expected allele frequency for a pathogenic variant in OBSL1 causing Three M Syndrome 2 phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. To our knowledge, no occurrence of c.2887G>A in individuals affected with Three M Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=2) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |