ClinVar Miner

Submissions for variant NM_024306.5(FA2H):c.103G>T (p.Asp35Tyr)

dbSNP: rs121918217
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV000001099 SCV003831165 likely pathogenic Hereditary spastic paraplegia 35 2022-09-06 criteria provided, single submitter clinical testing
3billion RCV000001099 SCV003841930 uncertain significance Hereditary spastic paraplegia 35 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with FA2H -related disorder (ClinVar ID: VCV000001044 / PMID: 19068277). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 19068277). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.
Breakthrough Genomics, Breakthrough Genomics RCV000001099 SCV005088805 pathogenic Hereditary spastic paraplegia 35 2020-01-30 criteria provided, single submitter clinical testing This variant is predicted to be damaging by in-silico missense prediction tools (SIFT and Polyphen2). The variant was previously reported in a consanguineous Arab-Muslim family (as c.103G→T and D35Y in the article) in the homozygous state and the patient was diagnosed with Leukodystrophy with Spastic Paraparesis and Dystonia [PMID: 19068277, 21592092, 24299421]. In-vitro functional studies revealed that the cells harboring the p.Asp35Tyr variant exhibited a significant reduction in endogenous FA2H enzymatic activity when compared to wild type cells suggesting its loss-of-function [PMID: 19068277].
OMIM RCV000001099 SCV000021249 pathogenic Hereditary spastic paraplegia 35 2008-11-01 no assertion criteria provided literature only

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.