Submissions for variant NM_001364905.1(LRBA):c.5518+2T>C

dbSNP: rs532289025

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003647015	SCV004557640	likely pathogenic	Combined immunodeficiency due to LRBA deficiency	2023-11-24	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 33 of the LRBA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LRBA are known to be pathogenic (PMID: 26206937, 26768763). This variant is present in population databases (rs532289025, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004750927	SCV005364515	likely pathogenic	LRBA-related disorder	2024-05-22	no assertion criteria provided	clinical testing	The LRBA c.5518+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of South Asian descent in gnomAD. Variants that disrupt the consensus splice donor site in LRBA are expected to be pathogenic. This variant is interpreted as likely pathogenic.