ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2731G>A (p.Gly911Ser)

gnomAD frequency: 0.00354  dbSNP: rs34302553
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000317403 SCV000331143 benign not specified 2015-07-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000870814 SCV001012360 benign Niemann-Pick disease, type C1 2024-01-29 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000870814 SCV001286844 benign Niemann-Pick disease, type C1 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV000870814 SCV001984544 benign Niemann-Pick disease, type C1 2020-03-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000317403 SCV002103435 benign not specified 2022-02-24 criteria provided, single submitter clinical testing Variant summary: NPC1 c.2731G>A (p.Gly911Ser) 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 0.00097 in 251484 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.0 fold of the estimated maximal expected allele frequency for a pathogenic variant in NPC1 causing Niemann-Pick Disease Type C phenotype (0.0027), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2731G>A in individuals affected with Niemann-Pick Disease Type C and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen RCV001579491 SCV004140859 benign not provided 2023-10-01 criteria provided, single submitter clinical testing NPC1: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics RCV001579491 SCV005251285 benign not provided criteria provided, single submitter not provided
Natera, Inc. RCV000870814 SCV001463702 benign Niemann-Pick disease, type C1 2020-05-04 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579491 SCV001807456 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000317403 SCV001966690 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001579491 SCV002034079 likely benign not provided no assertion criteria provided clinical testing

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