Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001042749 | SCV001206450 | uncertain significance | Bardet-Biedl syndrome | 2022-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 504 of the BBS4 protein (p.Ala504Val). This variant is present in population databases (rs150706579, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. ClinVar contains an entry for this variant (Variation ID: 840690). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Illumina Laboratory Services, |
RCV001118760 | SCV001277068 | uncertain significance | Bardet-Biedl syndrome 4 | 2018-03-02 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Fulgent Genetics, |
RCV001118760 | SCV002776665 | uncertain significance | Bardet-Biedl syndrome 4 | 2024-01-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004601334 | SCV005099052 | uncertain significance | Inborn genetic diseases | 2024-05-13 | criteria provided, single submitter | clinical testing | The c.1511C>T (p.A504V) alteration is located in exon 16 (coding exon 16) of the BBS4 gene. This alteration results from a C to T substitution at nucleotide position 1511, causing the alanine (A) at amino acid position 504 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003405233 | SCV004107442 | uncertain significance | BBS4-related disorder | 2024-05-16 | no assertion criteria provided | clinical testing | The BBS4 c.1511C>T variant is predicted to result in the amino acid substitution p.Ala504Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of Latino descent in gnomAD, which may be too common to be an undocumented pathogenic variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |