Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000616285 | SCV000712304 | uncertain significance | not specified | 2016-06-28 | criteria provided, single submitter | clinical testing | The p.Glu287X variant in BSND has not been previously reported in individuals wi th hearing loss or Bartter syndrome, but has been identified in 1/66718 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs376784896). Although this variant has been seen in the general p opulation, its frequency is not high enough to rule out a pathogenic role. This nonsense variant leads to a premature termination codon at position 287. This al teration occurs within the last exon and is likely to escape nonsense mediated d ecay (NMD) and to result in a truncated product 10% shorter than the normal prot ein. It is unclear whether the truncation impacts the protein function. In summa ry, the clinical significance of the p.Glu287X variant is uncertain. |
Illumina Laboratory Services, |
RCV000778246 | SCV000914417 | uncertain significance | Bartter disease type 4A | 2018-12-15 | criteria provided, single submitter | clinical testing | This variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. This variant is located in the last exon or in the last 50 bp of the penultimate exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
Invitae | RCV002529317 | SCV003452384 | uncertain significance | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu287*) in the BSND gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the BSND protein. This variant is present in population databases (rs376784896, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BSND-related conditions. ClinVar contains an entry for this variant (Variation ID: 505171). 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 | RCV002529318 | SCV003564276 | uncertain significance | Inborn genetic diseases | 2021-05-27 | criteria provided, single submitter | clinical testing | The c.859G>T (p.E287*) alteration, located in exon 4 (coding exon 4) of the BSND gene, consists of a G to T substitution at nucleotide position 859. This changes the amino acid from a glutamic acid (E) to a stop codon at amino acid position 287. Premature stop codons are typically deleterious in nature (Richards, 2015). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001829705 | SCV002092706 | uncertain significance | Bartter syndrome | 2020-12-15 | no assertion criteria provided | clinical testing |