Submissions for variant NM_000282.4(PCCA):c.627A>G (p.Ala209=)

gnomAD frequency: 0.14245  dbSNP: rs538229

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000180126	SCV000232508	benign	not specified	2014-06-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000180126	SCV000303458	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000392647	SCV000382011	benign	Propionic acidemia	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000180126	SCV000539993	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587997	SCV000696477	benign	not provided	2017-03-13	criteria provided, single submitter	clinical testing	Variant summary: The PCCA c.627A>G (p.Ala209Ala) variant involves the alteration of a conserved nucleotide causing a synonymous change that 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 17901/121368 control chromosomes (1483 homozygotes) at a frequency of 0.1474936, which is approximately 43 times the estimated maximal expected allele frequency for a pathogenic PCCA variant (0.003446), strong evidence that this variant is a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Invitae	RCV000392647	SCV001725436	benign	Propionic acidemia	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000392647	SCV001750046	benign	Propionic acidemia	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000587997	SCV001871468	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000392647	SCV002029405	benign	Propionic acidemia	2021-09-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000392647	SCV001455844	benign	Propionic acidemia	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000180126	SCV001923194	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000180126	SCV001958611	benign	not specified		no assertion criteria provided	clinical testing