chr2-232136511-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):āc.742A>Gā(p.Thr248Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,970 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T248I) 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.742A>G | p.Thr248Ala | missense_variant | 8/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.742A>G | p.Thr248Ala | missense_variant | 8/14 | ||
DIS3L2 | NR_046476.2 | n.888A>G | non_coding_transcript_exon_variant | 8/21 | |||
DIS3L2 | NR_046477.2 | n.1072+5568A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.742A>G | p.Thr248Ala | missense_variant | 8/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249312Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135254
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727180
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 248 of the DIS3L2 protein (p.Thr248Ala). This variant is present in population databases (rs766947723, gnomAD 0.003%). 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: 581239). 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