Submissions for variant NM_000376.3(VDR):c.1073G>A (p.Arg358His)

gnomAD frequency: 0.00106  dbSNP: rs114678556

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000901691	SCV001046074	benign	not provided	2025-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001112346	SCV001270000	uncertain significance	Vitamin D-dependent rickets type II with alopecia	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005236416	SCV005887546	benign	not specified	2025-01-24	criteria provided, single submitter	clinical testing	Variant summary: VDR c.1073G>A (p.Arg358His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0003 in 251270 control chromosomes, predominantly at a frequency of 0.0037 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in VDR causing Vitamin D-Dependent Rickets Type II With Alopecia phenotype. To our knowledge, no occurrence of c.1073G>A in individuals affected with Vitamin D-Dependent Rickets Type II With Alopecia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 727362). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003922981	SCV004744149	likely benign	VDR-related disorder	2022-05-11	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).