Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192974 | SCV001361468 | uncertain significance | not specified | 2019-03-13 | criteria provided, single submitter | clinical testing | Variant summary: UNC80 c.2281G>A (p.Gly761Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 178994 control chromosomes, predominantly observed within the Latino subpopulation at a frequency of 0.00073 (18/24774) in the gnomAD database; however this variant is indicated to be located in a low complexity region (LCR) region, which may indicate a low-quality site, therefore these data may not be reliable. To our knowledge, no occurrence of c.2281G>A in individuals affected with IHPRF2 (Infantile hypotonia with psychomotor retardation and characteristic facies 2) 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 uncertain significance. |
| Labcorp Genetics |
RCV001863053 | SCV002218880 | uncertain significance | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 761 of the UNC80 protein (p.Gly761Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with UNC80-related conditions. ClinVar contains an entry for this variant (Variation ID: 928694). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002560159 | SCV003545751 | uncertain significance | Inborn genetic diseases | 2024-09-04 | criteria provided, single submitter | clinical testing | The c.2281G>A (p.G761R) alteration is located in exon 13 (coding exon 13) of the UNC80 gene. This alteration results from a G to A substitution at nucleotide position 2281, causing the glycine (G) at amino acid position 761 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001863053 | SCV005628737 | uncertain significance | not provided | 2024-07-16 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |