ClinVar Miner

Submissions for variant NM_052867.4(NALCN):c.2495A>G (p.Tyr832Cys)

gnomAD frequency: 0.00003  dbSNP: rs549182297
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000934218 SCV001079936 likely benign not provided 2024-09-06 criteria provided, single submitter clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001731981 SCV001984610 likely benign not specified 2020-09-24 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000934218 SCV004236781 uncertain significance not provided 2023-10-26 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000934218 SCV001552993 uncertain significance not provided no assertion criteria provided clinical testing The NALCN p.Y832C variant was not identified in the literature but was identified in dbSNP (ID: rs549182297) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 176 of 282618 chromosomes (1 homozygous) at a frequency of 0.0006227, and was observed at the highest frequency in the South Asian population in 171 of 30614 chromosomes (1 homozygous) (freq: 0.005586) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.Y832 residue is conserved in mammals and more distantly related organisms, and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on 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.
PreventionGenetics, part of Exact Sciences RCV004533590 SCV004750371 likely benign NALCN-related disorder 2023-03-28 no assertion criteria provided 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).

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