Submissions for variant NM_006208.3(ENPP1):c.2462G>A (p.Arg821His)

gnomAD frequency: 0.00004  dbSNP: rs367759638

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000970455	SCV001118033	benign	not provided	2023-12-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153010	SCV001314253	uncertain significance	Hypophosphatemic rickets, autosomal recessive, 2	2017-04-27	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.
Illumina Laboratory Services, Illumina	RCV001153011	SCV001314254	uncertain significance	Arterial calcification, generalized, of infancy, 1	2017-04-27	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.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001153011	SCV001435268	benign	Arterial calcification, generalized, of infancy, 1		criteria provided, single submitter	research	The heterozygous p.Arg821His variant in ENPP1 has been identified in 3 Pakistani relatives from 1 family with idiopathic infantile arterial calcification, all of whom were also homozygous for p.Asp804His (PMID: 15605415), and has been identified in >1% of South Asian chromosomes and 6 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive idiopathic infantile arterial calcification.
PreventionGenetics, part of Exact Sciences	RCV004535956	SCV004719512	benign	ENPP1-related disorder	2024-01-26	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).