rs762363254
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152383.5(DIS3L2):c.1915G>A(p.Ala639Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A639P) 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.1915G>A | p.Ala639Thr | missense_variant | 15/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1582-13357G>A | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1988G>A | non_coding_transcript_exon_variant | 15/21 | |||
DIS3L2 | NR_046477.2 | n.1967G>A | non_coding_transcript_exon_variant | 14/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1915G>A | p.Ala639Thr | missense_variant | 15/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 244096Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132720
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1456666Hom.: 0 Cov.: 35 AF XY: 0.00000690 AC XY: 5AN XY: 724302
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2023 | ClinVar contains an entry for this variant (Variation ID: 531949). 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. 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. This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 639 of the DIS3L2 protein (p.Ala639Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at