Submissions for variant NM_002292.4(LAMB2):c.4118A>G (p.Asp1373Gly)

gnomAD frequency: 0.00076  dbSNP: rs112933248

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000559112	SCV000651552	uncertain significance	Pierson syndrome; LAMB2-related infantile-onset nephrotic syndrome	2022-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1373 of the LAMB2 protein (p.Asp1373Gly). This variant is present in population databases (rs112933248, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 472484). 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 glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Illumina Laboratory Services, Illumina	RCV001145299	SCV001305953	uncertain significance	LAMB2-related infantile-onset nephrotic syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001145300	SCV001305954	uncertain significance	Pierson syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001764596	SCV001999677	uncertain significance	not provided	2020-01-06	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20556798, 27573339)
CeGaT Center for Human Genetics Tuebingen	RCV001764596	SCV004154539	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	LAMB2: BP4
PreventionGenetics, part of Exact Sciences	RCV003952833	SCV004769690	likely benign	LAMB2-related condition	2023-12-05	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).