Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000249547 | SCV000314013 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
| Gene |
RCV000249547 | SCV000730145 | benign | not specified | 2017-03-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Labcorp Genetics |
RCV000870656 | SCV001012179 | benign | 3-methylcrotonyl-CoA carboxylase 2 deficiency | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000249547 | SCV002570936 | benign | not specified | 2022-07-01 | criteria provided, single submitter | clinical testing | Variant summary: MCCC2 c.282-7G>A 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 0.001 in 251392 control chromosomes (gnomAD), predominantly at a frequency of 0.013 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in MCCC2 causing Methylcrotonyl-CoA Carboxylase Deficiency phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.282-7G>A in individuals affected with Methylcrotonyl-CoA Carboxylase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
| Breakthrough Genomics, |
RCV004705114 | SCV005225579 | likely benign | not provided | criteria provided, single submitter | not provided |