Submissions for variant NM_015175.3(NBEAL2):c.3387G>A (p.Ala1129=)

gnomAD frequency: 0.00038  dbSNP: rs371065166

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000518982	SCV000620424	likely benign	not provided	2019-09-27	criteria provided, single submitter	clinical testing	In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235267	SCV003933928	uncertain significance	not specified	2023-05-22	criteria provided, single submitter	clinical testing	Variant summary: NBEAL2 c.3387G>A (p.Ala1129Ala) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant creates a cryptic 5' donor site and one predicts the variant strengthens the same cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00035 in 264918 control chromosomes (gnomAD), predominantly at a frequency of 0.0043 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. To our knowledge, no occurrence of c.3387G>A in individuals affected with Gray Platelet Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.