Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000287997 | SCV000480739 | likely benign | Chorea-acanthocytosis | 2018-01-13 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Athena Diagnostics | RCV000518625 | SCV000616260 | uncertain significance | not provided | 2018-03-14 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000287997 | SCV000897528 | uncertain significance | Chorea-acanthocytosis | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000518625 | SCV001001810 | likely benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000518625 | SCV001155654 | likely benign | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | VPS13A: BP4, BS2 |
Baylor Genetics | RCV000287997 | SCV001521050 | uncertain significance | Chorea-acanthocytosis | 2020-12-29 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV000518625 | SCV001820073 | likely benign | not provided | 2022-07-21 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Prevention |
RCV003912582 | SCV004741886 | likely benign | VPS13A-related disorder | 2020-09-16 | criteria provided, single submitter | 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). |
Diagnostic Laboratory, |
RCV000287997 | SCV000734704 | likely benign | Chorea-acanthocytosis | no assertion criteria provided | clinical testing | ||
Department of Pathology and Laboratory Medicine, |
RCV000518625 | SCV001554009 | likely benign | not provided | no assertion criteria provided | clinical testing | The VPS13A p.Asn259Asp variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs41307461), LOVD 3.0 (classified as likely benign) and in ClinVar (classified as a VUS by Illumina, Athena Diagnostics and Fulgent Genetics and as likely benign by Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen). The variant was also identified in control databases in 705 of 282532 chromosomes (2 homozygous) at a frequency of 0.002495 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 567 of 128988 chromosomes (freq: 0.004396), Ashkenazi Jewish in 41 of 10364 chromosomes (freq: 0.003956), Other in 23 of 7206 chromosomes (freq: 0.003192), European (Finnish) in 37 of 25112 chromosomes (freq: 0.001473), African in 18 of 24922 chromosomes (freq: 0.000722) and Latino in 19 of 35392 chromosomes (freq: 0.000537), but not in the East Asian and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Asn259 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. | |
Genome Diagnostics Laboratory, |
RCV000518625 | SCV001807897 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000518625 | SCV001972993 | likely benign | not provided | no assertion criteria provided | clinical testing |