2-232136679-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_152383.5(DIS3L2):c.910C>T(p.Arg304Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R304H) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.910C>T | p.Arg304Cys | missense_variant | 8/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.910C>T | p.Arg304Cys | missense_variant | 8/14 | ||
DIS3L2 | NR_046476.2 | n.1056C>T | non_coding_transcript_exon_variant | 8/21 | |||
DIS3L2 | NR_046477.2 | n.1072+5736C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.910C>T | p.Arg304Cys | missense_variant | 8/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152018Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249226Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135198
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461742Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36AN XY: 727170
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74350
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 304 of the DIS3L2 protein (p.Arg304Cys). This variant is present in population databases (rs149157216, gnomAD 0.03%). 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: 410767). 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 not expected to disrupt DIS3L2 protein function with a negative 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