Submissions for variant NM_000022.4(ADA):c.613_615del (p.Val205del)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003388750	SCV004100512	uncertain significance	Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency		criteria provided, single submitter	clinical testing	The in-frame deletion p.V205del in ADA (NM_000022.3) has been reported previously in compound heterozygous state along with a 3' splice variant in patient of Indian ethinicity with T-,B-,NK- SCID (Aluri J et al,2019), however functional analysis was not performed. The p.V205del variant is observed in 3/1,13,602 (0.0026%) alleles from individuals of European (Non-Finnish) background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant results in a deletion of a valine at position 205 of the ADA gene. However, as this is an in-frame deletion, it is not expected to result in either a truncated protein product or loss of protein through nonsense-mediated mRNA decay. The p.V205del variant is not in a repeat region. The p.V205del variant results in a deletion of 3 bases that are predicted conserved by GERP++ and PhyloP. The nucleotide c.613 in ADA is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.