Submissions for variant NM_001364905.1(LRBA):c.5030A>G (p.Asn1677Ser)

gnomAD frequency: 0.00349  dbSNP: rs17027133

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079811	SCV000772282	benign	Combined immunodeficiency due to LRBA deficiency	2024-01-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727921	SCV000855430	benign	not specified	2017-06-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757439	SCV000885663	uncertain significance	not provided	2017-10-31	criteria provided, single submitter	clinical testing	Although the p.Asn1677Ser variant (rs17027133) has not been reported in the medical literature, it is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.99% in the African population (identified in 238 out of 24,032 chromosomes). The asparagine at codon 1677 is moderately conserved considering 13 species (Alamut software v2.10.0), and computational analyses predict that this variant does affect the structure/function of the LRBA protein (SIFT: damaging, PolyPhen2: probably damaging, MutationTaster: disease causing). However, based on the available information, the clinical significance of the p.Asn1677Ser variant cannot be determined with certainty.
Genetic Services Laboratory, University of Chicago	RCV000727921	SCV002064848	benign	not specified	2021-01-04	criteria provided, single submitter	clinical testing
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	RCV001079811	SCV002525558	uncertain significance	Combined immunodeficiency due to LRBA deficiency	2022-05-17	criteria provided, single submitter	clinical testing	The c.5030A>G variant is present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and Indian Exome Database, at a low frequency. The variant is also present in our in-house exome database. The variant was previously reported to ClinVar (Accession: VCV000540408.9) with conflicitng interpretations of pathogenicity (Uncertain significane/benign) in association with combined immunodeficiency due to LRBA deficiency. In-silico pathogenicity prediction programs like SIFT, PolyPhen-2, MutationTaster2, CADD predicted this variant to be likely deleterious, however these predictions were not confirmed by any published functional studies.
CeGaT Center for Human Genetics Tuebingen	RCV000757439	SCV002544908	benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	LRBA: BS1, BS2
Genetics and Molecular Pathology, SA Pathology	RCV001079811	SCV002761382	uncertain significance	Combined immunodeficiency due to LRBA deficiency	2019-10-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937963	SCV004756560	likely benign	LRBA-related disorder	2020-06-09	no assertion criteria provided	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).