5-35860850-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_002185.5(IL7R):c.83-2A>G variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00000684 in 1,461,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002185.5 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251156Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135738
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461108Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726888
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Immunodeficiency 104 Uncertain:1
The IL7R c.83-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. It has been reported in a compound heterozygous state in one individual with severe combined immune deficiency (Felgentreff et al. 2011). Control data are unavailable for this variant, and it is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium despite being found in a region with good sequencing coverage. The variant is thus presumed to be rare. Based on the limited evidence and the potential impact of splice acceptor variants, the c.83-2A>G variant is classified as a variant of unknown significance but suspicious for pathogenicity for severe combined immune deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at