rs1296826867
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152383.5(DIS3L2):āc.1703A>Gā(p.Gln568Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
DIS3L2
NM_152383.5 missense
NM_152383.5 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 5.71
Genes affected
DIS3L2 (HGNC:28648): (DIS3 like 3'-5' exoribonuclease 2) The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19626224).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIS3L2 | NM_152383.5 | c.1703A>G | p.Gln568Arg | missense_variant | 14/21 | ENST00000325385.12 | NP_689596.4 | |
DIS3L2 | NM_001257281.2 | c.1581+36721A>G | intron_variant | NP_001244210.1 | ||||
DIS3L2 | NR_046476.2 | n.1849A>G | non_coding_transcript_exon_variant | 14/21 | ||||
DIS3L2 | NR_046477.2 | n.1825A>G | non_coding_transcript_exon_variant | 13/19 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249052Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135110
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461644Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727110
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Perlman syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 568 of the DIS3L2 protein (p.Gln568Arg). This variant is present in population databases (no rsID available, gnomAD no frequency). 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: 463067). 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 with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 30, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2023 | The c.1703A>G (p.Q568R) alteration is located in exon 14 (coding exon 13) of the DIS3L2 gene. This alteration results from a A to G substitution at nucleotide position 1703, causing the glutamine (Q) at amino acid position 568 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
D;D;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Gain of catalytic residue at Q568 (P = 0.0801);Gain of catalytic residue at Q568 (P = 0.0801);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at