chr20-44636226-C-G
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000022.4(ADA):c.95+1G>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000249 in 1,609,542 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_000022.4 splice_donor, intron
Scores
Clinical Significance
Conservation
Publications
- severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
- Omenn syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADA | NM_000022.4 | c.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 11 | ENST00000372874.9 | NP_000013.2 | ||
ADA | NM_001322051.2 | c.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 10 | NP_001308980.1 | |||
ADA | NM_001322050.2 | c.-195+1G>C | splice_donor_variant, intron_variant | Intron 2 of 10 | NP_001308979.1 | |||
ADA | NR_136160.2 | n.187+1G>C | splice_donor_variant, intron_variant | Intron 2 of 10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADA | ENST00000372874.9 | c.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 11 | 1 | NM_000022.4 | ENSP00000361965.4 | |||
ADA | ENST00000695995.1 | c.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 8 | ENSP00000512318.1 | |||||
ADA | ENST00000695991.1 | c.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 7 | ENSP00000512314.1 | |||||
ADA | ENST00000696038.1 | n.95+1G>C | splice_donor_variant, intron_variant | Intron 2 of 8 | ENSP00000512344.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000817 AC: 2AN: 244702 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457410Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724678 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296 show subpopulations
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at