Submissions for variant NM_080425.4(GNAS):c.154G>A (p.Glu52Lys)

gnomAD frequency: 0.00022  dbSNP: rs527488103

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002488395	SCV002789618	uncertain significance	McCune-Albright syndrome; Pseudohypoparathyroidism type 1C; Pseudohypoparathyroidism type 1B; Pseudopseudohypoparathyroidism; Progressive osseous heteroplasia; Pituitary adenoma 3, multiple types; ACTH-independent macronodular adrenal hyperplasia 1; Pseudohypoparathyroidism type I A	2022-04-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004536205	SCV004116531	uncertain significance	GNAS-related disorder	2023-09-11	criteria provided, single submitter	clinical testing	The GNAS c.154G>A variant is predicted to result in the amino acid substitution p.Glu52Lys. This variant can also be referred to as precoding variant c.-38308G>A with an alternative transcript (NM_000516). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.041% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-57428474-G-A), which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics	RCV004039388	SCV004877044	likely benign	Inborn genetic diseases	2022-05-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572791	SCV001797705	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001572791	SCV001974467	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001572791	SCV001978859	uncertain significance	not provided		no assertion criteria provided	clinical testing