Submissions for variant NM_006118.4(HAX1):c.221G>A (p.Arg74His)

gnomAD frequency: 0.00004  dbSNP: rs151225652

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001281016	SCV001468420	uncertain significance	Kostmann syndrome	2021-03-30	criteria provided, single submitter	clinical testing	HAX1 NM_006118.3 exon 2 p.Arg74His (c.221G>A): This variant has not been reported in the literature but is present in 0.04% (10/24972) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-154245979-G-A?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics	RCV004978239	SCV005596182	uncertain significance	Inborn genetic diseases	2024-12-02	criteria provided, single submitter	clinical testing	The p.R74H variant (also known as c.221G>A), located in coding exon 2 of the HAX1 gene, results from a G to A substitution at nucleotide position 221. The arginine at codon 74 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.