Submissions for variant NM_002292.4(LAMB2):c.2945G>A (p.Arg982Gln)

gnomAD frequency: 0.00006  dbSNP: rs149653966

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000700025	SCV000828761	uncertain significance	Pierson syndrome; LAMB2-related infantile-onset nephrotic syndrome	2022-07-11	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 577310). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. This variant is present in population databases (rs149653966, gnomAD 0.2%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 982 of the LAMB2 protein (p.Arg982Gln).
Fulgent Genetics, Fulgent Genetics	RCV000700025	SCV002779783	uncertain significance	Pierson syndrome; LAMB2-related infantile-onset nephrotic syndrome	2022-03-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003953244	SCV004777355	likely benign	LAMB2-related condition	2022-03-21	criteria provided, single submitter	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).