Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002318848 | SCV000850285 | uncertain significance | Inborn genetic diseases | 2016-10-28 | criteria provided, single submitter | clinical testing | The c.10017+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 53 in the VPS13B gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV001349899 | SCV001544265 | uncertain significance | Cohen syndrome | 2022-10-08 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 54 of the VPS13B gene. It does not directly change the encoded amino acid sequence of the VPS13B protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs772319548, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 589438). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Natera, |
RCV001349899 | SCV002082727 | uncertain significance | Cohen syndrome | 2020-10-09 | no assertion criteria provided | clinical testing |