Submissions for variant NM_032575.3(GLIS2):c.1177G>A (p.Gly393Arg)

gnomAD frequency: 0.00009  dbSNP: rs759416922

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001115632	SCV001273626	uncertain significance	Nephronophthisis 7	2018-01-13	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.
Fulgent Genetics, Fulgent Genetics	RCV001115632	SCV002779771	uncertain significance	Nephronophthisis 7	2022-03-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002556272	SCV003274720	uncertain significance	Nephronophthisis	2024-08-29	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 393 of the GLIS2 protein (p.Gly393Arg). This variant is present in population databases (rs759416922, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with GLIS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 884520). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV003480962	SCV004227520	uncertain significance	not provided	2022-12-07	criteria provided, single submitter	clinical testing	BP4
Ambry Genetics	RCV004032194	SCV004876251	uncertain significance	not specified	2023-12-14	criteria provided, single submitter	clinical testing	The c.1177G>A (p.G393R) alteration is located in exon 6 (coding exon 6) of the GLIS2 gene. This alteration results from a G to A substitution at nucleotide position 1177, causing the glycine (G) at amino acid position 393 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV003480962	SCV005194191	uncertain significance	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003918699	SCV004727856	uncertain significance	GLIS2-related disorder	2024-09-03	no assertion criteria provided	clinical testing	The GLIS2 c.1177G>A variant is predicted to result in the amino acid substitution p.Gly393Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.051% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.