rs779500558
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_152383.5(DIS3L2):c.1807G>A(p.Glu603Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000352 in 1,421,104 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. E603E) has been classified as Likely benign.
Frequency
Consequence
NM_152383.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1807G>A | p.Glu603Lys | missense_variant | 15/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1582-13465G>A | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1886-6G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | ||||
DIS3L2 | NR_046477.2 | n.1862-3G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1807G>A | p.Glu603Lys | missense_variant | 15/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000383 AC: 5AN: 130518Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000284 AC: 7AN: 246282Hom.: 1 AF XY: 0.0000298 AC XY: 4AN XY: 134080
GnomAD4 exome AF: 0.0000349 AC: 45AN: 1290586Hom.: 2 Cov.: 36 AF XY: 0.0000422 AC XY: 27AN XY: 640034
GnomAD4 genome ? AF: 0.0000383 AC: 5AN: 130518Hom.: 0 Cov.: 32 AF XY: 0.0000162 AC XY: 1AN XY: 61602
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 603 of the DIS3L2 protein (p.Glu603Lys). This variant is present in population databases (rs779500558, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. 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: 576191). 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. 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