Submissions for variant NM_000282.4(PCCA):c.1429+7A>G

gnomAD frequency: 0.01356  dbSNP: rs16957276

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174996	SCV000226413	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000174996	SCV000303451	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000370381	SCV000382016	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000174996	SCV000514037	benign	not specified	2018-03-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174996	SCV000917966	benign	not specified	2018-01-05	criteria provided, single submitter	clinical testing	Variant summary: The PCCA c.1429+7A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 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 4420/277054 control chromosomes (51 homozygotes) at a frequency of 0.0159536, which is approximately 5 times the estimated maximal expected allele frequency of a pathogenic PCCA variant (0.003446), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000370381	SCV001159143	benign	Propionic acidemia	2021-11-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000370381	SCV001728431	benign	Propionic acidemia	2025-02-02	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004703443	SCV005217662	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000370381	SCV001455849	benign	Propionic acidemia	2020-09-16	no assertion criteria provided	clinical testing