chr2-232263399-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152383.5(DIS3L2):c.1618C>T(p.Arg540Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R540H) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1618C>T | p.Arg540Cys | missense_variant | 13/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1581+37C>T | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1764C>T | non_coding_transcript_exon_variant | 13/21 | |||
DIS3L2 | NR_046477.2 | n.1740C>T | non_coding_transcript_exon_variant | 12/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1618C>T | p.Arg540Cys | missense_variant | 13/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249162Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135192
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727242
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74458
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 540 of the DIS3L2 protein (p.Arg540Cys). This variant is present in population databases (rs573031156, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. ClinVar contains an entry for this variant (Variation ID: 463064). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DIS3L2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at