ClinVar Miner

Submissions for variant NM_033305.3(VPS13A):c.775A>G (p.Asn259Asp)

gnomAD frequency: 0.00255  dbSNP: rs41307461
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina 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 Inc RCV000518625 SCV000616260 uncertain significance not provided 2018-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics, 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
CeGaT Center for Human Genetics Tuebingen RCV000518625 SCV001155654 likely benign not provided 2023-08-01 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].
GeneDx RCV000518625 SCV001820073 likely benign not provided 2022-07-21 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000287997 SCV000734704 likely benign Chorea-acanthocytosis no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System 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, Amsterdam University Medical Center RCV000518625 SCV001807897 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000518625 SCV001972993 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.