NM_152383.5:c.1406C>T
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):c.1406C>T(p.Thr469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T469T) has been classified as Likely benign.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
Publications
- Perlman syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1406C>T | p.Thr469Ile | missense_variant | Exon 12 of 21 | ENST00000325385.12 | NP_689596.4 | |
DIS3L2 | NM_001257281.2 | c.1406C>T | p.Thr469Ile | missense_variant | Exon 12 of 14 | NP_001244210.1 | ||
DIS3L2 | NR_046476.2 | n.1552C>T | non_coding_transcript_exon_variant | Exon 12 of 21 | ||||
DIS3L2 | NR_046477.2 | n.1528C>T | non_coding_transcript_exon_variant | Exon 11 of 19 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 249780 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727204 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74516 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 469 of the DIS3L2 protein (p.Thr469Ile). This variant is present in population databases (rs369229385, gnomAD 0.007%). 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: 566638). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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