rs775814377
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):c.1923T>A(p.Asn641Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1923T>A | p.Asn641Lys | missense_variant, splice_region_variant | 15/21 | ENST00000325385.12 | NP_689596.4 | |
DIS3L2 | NM_001257281.2 | c.1582-13349T>A | intron_variant | NP_001244210.1 | ||||
DIS3L2 | NR_046476.2 | n.1996T>A | splice_region_variant, non_coding_transcript_exon_variant | 15/21 | ||||
DIS3L2 | NR_046477.2 | n.1975T>A | splice_region_variant, non_coding_transcript_exon_variant | 14/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIS3L2 | ENST00000325385.12 | c.1923T>A | p.Asn641Lys | missense_variant, splice_region_variant | 15/21 | 5 | NM_152383.5 | ENSP00000315569 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453802Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 722504
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Perlman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 13, 2019 | This sequence change replaces asparagine with lysine at codon 641 of the DIS3L2 protein (p.Asn641Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. 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 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DIS3L2-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at