Submissions for variant NM_012414.4(RAB3GAP2):c.1205C>G (p.Thr402Arg)

gnomAD frequency: 0.00001  dbSNP: rs763764406

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000338576	SCV000354499	uncertain significance	Warburg micro syndrome 2	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000391809	SCV000354500	uncertain significance	Martsolf syndrome	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003993920	SCV004813027	uncertain significance	not specified	2024-02-16	criteria provided, single submitter	clinical testing	Variant summary: RAB3GAP2 c.1205C>G (p.Thr402Arg) results in a non-conservative amino acid change located in the Rab3-GAP regulatory subunit, N-terminal (IPR032839) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 250974 control chromosomes. To our knowledge, no occurrence of c.1205C>G in individuals affected with RAB3GAP2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 295661). Based on the evidence outlined above, the variant was classified as uncertain significance.
GenomeConnect - CFC International	RCV004776282	SCV001156339	not provided	Warburg micro syndrome 2; Martsolf syndrome 1		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 09-18-2012 by Lab Baylor Genetics. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.