Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226836 | SCV003923152 | benign | not specified | 2023-03-15 | criteria provided, single submitter | clinical testing | Variant summary: PLEKHG5 c.2160_2163delinsA (p.Glu723del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was not found in gnomAD but the same residual change (p.Glu72del) at a frequency of 0.088 in 145232 control chromosomes, predominantly at a frequency of 0.18 within the African or African-American subpopulation in the gnomAD database, including 509 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 161 fold of the estimated maximal expected allele frequency for a pathogenic variant in PLEKHG5 causing Distal Spinal Muscular Atrophy, Autosomal Recessive 4 phenotype (0.0011), 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.2160_2163delinsA in individuals affected with Distal Spinal Muscular Atrophy, Autosomal Recessive 4 and no experimental evidence demonstrating its impact on protein function have been reported. 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 benign. Based on the evidence outlined above, the variant was classified as benign. |
| Gene |
RCV004765779 | SCV005379265 | uncertain significance | not provided | 2024-04-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acids in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge |