rs1060503032
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):c.2425A>C(p.Lys809Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K809N) 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.2425A>C | p.Lys809Gln | missense_variant | 20/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1582-7542A>C | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.2498A>C | non_coding_transcript_exon_variant | 20/21 | |||
DIS3L2 | NR_046477.2 | n.2477A>C | non_coding_transcript_exon_variant | 19/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.2425A>C | p.Lys809Gln | missense_variant | 20/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1398366Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 689696
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2019 | 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This sequence change replaces lysine with glutamine at codon 809 of the DIS3L2 protein (p.Lys809Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at