Submissions for variant NM_021942.6(TRAPPC11):c.2147C>G (p.Ala716Gly)

gnomAD frequency: 0.00064  dbSNP: rs143990563

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000858939	SCV000615834	benign	not provided	2018-10-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531617	SCV000654272	likely benign	Autosomal recessive limb-girdle muscular dystrophy type R18	2024-01-22	criteria provided, single submitter	clinical testing
NeuroMeGen, Hospital Clinico Santiago de Compostela	RCV000531617	SCV000882629	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type R18	2018-10-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000531617	SCV001529312	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type R18	2018-02-08	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000858939	SCV001785750	likely benign	not provided	2021-01-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782420	SCV005394345	likely benign	not specified	2024-09-16	criteria provided, single submitter	clinical testing	Variant summary: TRAPPC11 c.2147C>G (p.Ala716Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00058 in 251116 control chromosomes, predominantly at a frequency of 0.00076 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.05 fold of the estimated maximal expected allele frequency for a pathogenic variant in TRAPPC11 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.00072). c.2147C>G has been reported in the literature in an individual suspected of a neuromuscular disease without a conclusive diagnosis (Barbosa-Gouveia_2022). This report does not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35628876). ClinVar contains an entry for this variant (Variation ID: 448695). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003915462	SCV004736306	likely benign	TRAPPC11-related disorder	2022-05-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).