ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.4893C>G (p.Asp1631Glu)

gnomAD frequency: 0.00014  dbSNP: rs201296719
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502380 SCV000596761 uncertain significance not specified 2015-11-05 criteria provided, single submitter clinical testing
Invitae RCV000692250 SCV000820063 benign Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2024-01-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001354653 SCV002062777 uncertain significance not provided 2021-12-01 criteria provided, single submitter clinical testing
GeneDx RCV001354653 SCV002559526 uncertain significance not provided 2022-08-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24448499, 30181556, 28404951)
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354653 SCV001549319 uncertain significance not provided no assertion criteria provided clinical testing The RELN p.Asp1631Glu variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs201296719, Uncertain significance) and in ClinVar (classified as a VUS by the Genetic Services Laboratory at the University of Chicago in 2015 and by Invitae in 2018). The variant was identified in control databases in 29 of 282000 chromosomes at a frequency of 0.000103 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 15 of 10342 chromosomes (freq: 0.00145), Other in 3 of 7196 chromosomes (freq: 0.000417), Latino in 7 of 35390 chromosomes (freq: 0.000198) and European (non-Finnish) in 4 of 128492 chromosomes (freq: 0.000031); it was not observed in the African, East Asian, European (Finnish), and South Asian populations. The p.Asp1631 residue is conserved in mammals and other organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. 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. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.