ENST00000359785.10:c.1894+2T>C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The ENST00000359785.10(PTPN22):c.1894+2T>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000997 in 1,404,664 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
ENST00000359785.10 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPN22 | NM_015967.8 | c.1894+2T>C | splice_donor_variant, intron_variant | Intron 14 of 20 | NP_057051.4 | |||
PTPN22 | NM_001308297.2 | c.1822+2T>C | splice_donor_variant, intron_variant | Intron 13 of 19 | NP_001295226.2 | |||
PTPN22 | NM_001193431.3 | c.1894+2T>C | splice_donor_variant, intron_variant | Intron 14 of 20 | NP_001180360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPN22 | ENST00000359785.10 | c.1894+2T>C | splice_donor_variant, intron_variant | Intron 14 of 20 | 1 | ENSP00000352833.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000904 AC: 2AN: 221152Hom.: 0 AF XY: 0.00000828 AC XY: 1AN XY: 120764
GnomAD4 exome AF: 0.00000997 AC: 14AN: 1404664Hom.: 0 Cov.: 28 AF XY: 0.0000114 AC XY: 8AN XY: 700258
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rheumatoid arthritis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The splice site c.1894+2T>C variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with the allele frequency of 0.0009044% in gnomAD and is novel (not in any individuals) in 1000 Genomes. The nucleotide change in PTPN22 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at