Submissions for variant NM_000303.3(PMM2):c.712C>T (p.Arg238Cys)

gnomAD frequency: 0.00003  dbSNP: rs142459706

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000871793	SCV001013506	likely benign	PMM2-congenital disorder of glycosylation	2024-01-29	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000871793	SCV001984667	likely benign	PMM2-congenital disorder of glycosylation	2020-03-26	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000871793	SCV002495898	uncertain significance	PMM2-congenital disorder of glycosylation	2022-01-27	criteria provided, single submitter	clinical testing	PMM2 NM_000303.2 exon 8 p.Arg238Cys (c.712C>T): This variant has not been reported in the literature but is present in 0.8% (251/30612) of South Asian alleles including 2 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-8941653-C-T?dataset=gnomad_r2_1). This variant amino acid Cysteine (Cys) is present in multiple species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools are unclear. This variant is present in ClinVar, with multiple labs classifying this variant as Likely Benign (Variation ID:702628). However, other variants at this position have been reported in association with disease (p.Arg238Pro, p.Arg238His) suggesting that this codon may have functional significance. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Natera, Inc.	RCV000871793	SCV002092455	benign	PMM2-congenital disorder of glycosylation	2020-04-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003948174	SCV004762637	benign	PMM2-related disorder	2024-01-29	no assertion criteria provided	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).