Submissions for variant NM_001374353.1(GLI2):c.1751A>G (p.Asn584Ser)

gnomAD frequency: 0.00254  dbSNP: rs61732851

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000300246	SCV000416191	benign	Holoprosencephaly 9	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000864265	SCV001005043	benign	Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome	2023-10-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323517	SCV004028919	benign	not specified	2023-07-12	criteria provided, single submitter	clinical testing	Variant summary: GLI2 c.1802A>G (p.Asn601Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00059 in 254798 control chromosomes, predominantly at a frequency of 0.0085 within the African or African-American subpopulation in the gnomAD database. To our knowledge, no occurrence of c.1802A>G in individuals affected with GLI2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. The following publication has been ascertained in the context of this evaluation (PMID: 26334177). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV003430829	SCV004149103	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	GLI2: BS1
PreventionGenetics, part of Exact Sciences	RCV003922412	SCV004738879	benign	GLI2-related condition	2023-12-18	criteria provided, single submitter	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).