Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hudson |
RCV000258922 | SCV000328693 | likely pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 | 2016-10-13 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV000963427 | SCV001110579 | likely benign | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000258922 | SCV001136157 | uncertain significance | Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV001252621 | SCV001437903 | likely pathogenic | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
Centre de Biologie Pathologie Génétique, |
RCV002274004 | SCV002559059 | likely pathogenic | Neurodevelopmental delay | criteria provided, single submitter | clinical testing | ||
Victorian Clinical Genetics Services, |
RCV000258922 | SCV002768725 | likely benign | Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 | 2022-09-02 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_032504.1(UNC80):c.1806G>C, has been identified in exon 12 of 64 of the UNC80 gene. The variant is predicted to result in a minor amino acid change from glutamine to histidine at position 602 of the protein (NP_115893.1(UNC80):p.(Gln602His)). The glutamine residue at this position has high conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.14% (271 heterozygotes, 1 homozygote). The variant has been previously described as likely pathogenic (ClinVar, Decipher) and also VUS (EGL Genetics). Based on the information available at the time of curation, this variant has been classified as LIKELY BENIGN. |
Ambry Genetics | RCV002518797 | SCV003617325 | likely benign | Inborn genetic diseases | 2021-03-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Revvity Omics, |
RCV000258922 | SCV003828044 | uncertain significance | Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 | 2019-08-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987484 | SCV004804097 | likely benign | not specified | 2024-01-03 | criteria provided, single submitter | clinical testing | Variant summary: UNC80 c.1806G>C (p.Gln602His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 158532 control chromosomes in the gnomAD database, including 1 homozygotes. c.1806G>C has been reported in the literature in individuals with neurodevelopmental disorders or unaffected individuals. These report(s) do not provide unequivocal conclusions about association of the variant with Infantile Hypotonia With Psychomotor Retardation And Characteristic Facies 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31589614, 29158550). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign. |
Centre de Biologie Pathologie Génétique, |
RCV001252621 | SCV001428382 | uncertain significance | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004535244 | SCV004724952 | likely benign | UNC80-related disorder | 2021-01-18 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |