rs555184370
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_152383.5(DIS3L2):c.1740G>T(p.Lys580Asn) variant causes a missense, splice region change. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. K580R) has been classified as Uncertain significance.
Frequency
Consequence
NM_152383.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1740G>T | p.Lys580Asn | missense_variant, splice_region_variant | 15/21 | ENST00000325385.12 | |
DIS3L2 | NM_001257281.2 | c.1582-13532G>T | intron_variant | ||||
DIS3L2 | NR_046476.2 | n.1886-73G>T | intron_variant, non_coding_transcript_variant | ||||
DIS3L2 | NR_046477.2 | n.1862-70G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1740G>T | p.Lys580Asn | missense_variant, splice_region_variant | 15/21 | 5 | NM_152383.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 139548Hom.: 0 Cov.: 31 FAILED QC
GnomAD4 exome AF: 0.00000492 AC: 2AN: 406176Hom.: 0 Cov.: 10 AF XY: 0.00000474 AC XY: 1AN XY: 210992
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000716 AC: 1AN: 139696Hom.: 0 Cov.: 31 AF XY: 0.0000148 AC XY: 1AN XY: 67688
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 463073). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 580 of the DIS3L2 protein (p.Lys580Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at