Submissions for variant NM_002296.4(LBR):c.866G>A (p.Gly289Glu)

gnomAD frequency: 0.00171  dbSNP: rs148541545

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202858	SCV000257915	uncertain significance	not specified	2015-06-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000766850	SCV000618753	uncertain significance	not provided	2017-07-07	criteria provided, single submitter	clinical testing	The G289E variant in the LBR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G289E variant is observed in 51/7076 (0.72%) alleles from individuals of African background in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G289E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G289E as a variant of uncertain significance.
Invitae	RCV000766850	SCV001066756	benign	not provided	2024-01-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001098727	SCV001255113	likely benign	Greenberg dysplasia	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000766850	SCV001474289	uncertain significance	not provided	2020-04-21	criteria provided, single submitter	clinical testing	The LBR c.866G>A; p.Gly289Glu variant (rs148541545), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 218605). This variant is found in the African population with an allele frequency of 0.55% (130/23,638 alleles) in the Genome Aggregation Database. The glycine at codon 289 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of this variant is uncertain at this time.
PreventionGenetics, part of Exact Sciences	RCV003967543	SCV004778204	likely benign	LBR-related condition	2021-07-15	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).