Submissions for variant NM_000303.3(PMM2):c.324G>A (p.Ala108=)

gnomAD frequency: 0.01239  dbSNP: rs62031146

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000117997	SCV000257665	benign	not specified	2015-06-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000117997	SCV000303550	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000554451	SCV000399671	benign	PMM2-congenital disorder of glycosylation	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.
GeneDx	RCV000117997	SCV000517828	benign	not specified	2016-02-23	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554451	SCV000633724	benign	PMM2-congenital disorder of glycosylation	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000117997	SCV000920010	benign	not specified	2017-09-25	criteria provided, single submitter	clinical testing	Variant summary: The PMM2 c.324G>A (p.Ala108Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2137/121286 control chromosomes at a frequency of 0.0176195, which is approximately 3 times the estimated maximal expected allele frequency of a pathogenic PMM2 variant (0.0055902), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV000554451	SCV002811940	benign	PMM2-congenital disorder of glycosylation	2021-09-21	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004714455	SCV005296598	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000117997	SCV000152315	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000554451	SCV000733547	benign	PMM2-congenital disorder of glycosylation		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000554451	SCV001457167	benign	PMM2-congenital disorder of glycosylation	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000117997	SCV001922761	benign	not specified		no assertion criteria provided	clinical testing