rs1553606103
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152383.5(DIS3L2):c.376C>T(p.Pro126Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P126L) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.376C>T | p.Pro126Ser | missense_variant | 6/21 | ENST00000325385.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.376C>T | p.Pro126Ser | missense_variant | 6/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1458822Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725392
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 17, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DIS3L2-related disease. This sequence change replaces proline with serine at codon 126 of the DIS3L2 protein (p.Pro126Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at