Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV002247539 | SCV002517742 | benign | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000146689 | SCV003247417 | uncertain significance | Cornelia de Lange syndrome 1 | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 2160 of the NIPBL protein (p.Asp2160Tyr). This variant is present in population databases (rs147054690, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NIPBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 159195). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NIPBL protein function. 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 | RCV002512579 | SCV003678961 | likely benign | Inborn genetic diseases | 2022-11-09 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002247539 | SCV003934189 | uncertain significance | not specified | 2023-05-04 | criteria provided, single submitter | clinical testing | Variant summary: NIPBL c.6478G>T (p.Asp2160Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251388 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6478G>T in individuals affected with Cornelia De Lange Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance, one as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genetic Services Laboratory, |
RCV000146689 | SCV000194002 | likely pathogenic | Cornelia de Lange syndrome 1 | 2013-02-08 | flagged submission | clinical testing |