Submissions for variant NM_001378615.1(CC2D2A):c.1162G>A (p.Val388Ile)

gnomAD frequency: 0.00089  dbSNP: rs115924432

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000597954	SCV000705529	likely benign	not specified	2017-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001697392	SCV000721721	likely benign	not provided	2021-05-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636967	SCV000758415	likely benign	Familial aplasia of the vermis; Meckel-Gruber syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000597954	SCV002766131	uncertain significance	not specified	2022-11-27	criteria provided, single submitter	clinical testing	Variant summary: CC2D2A c.1162G>A (p.Val388Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00056 in 278974 control chromosomes (gnomAD), predominantly at a frequency of 0.0027 within the African or African-American subpopulation in the gnomAD database. To our knowledge, no occurrence of c.1162G>A in individuals affected with CC2D2A-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed the variant since 2014 without evidence for independent evaluation: all three classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV001697392	SCV004701292	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CC2D2A: BP4, BS1
PreventionGenetics, part of Exact Sciences	RCV004530693	SCV004748680	likely benign	CC2D2A-related disorder	2022-05-21	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).