2-232014955-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152383.5(DIS3L2):​c.28C>G​(p.Leu10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L10F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DIS3L2
NM_152383.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.785
Variant links:
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=0.074110806).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DIS3L2NM_152383.5 linkc.28C>G p.Leu10Val missense_variant Exon 2 of 21 ENST00000325385.12 NP_689596.4 Q8IYB7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DIS3L2ENST00000325385.12 linkc.28C>G p.Leu10Val missense_variant Exon 2 of 21 5 NM_152383.5 ENSP00000315569.7 Q8IYB7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
11
DANN
Benign
0.82
DEOGEN2
Benign
0.0081
.;T;.;T;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.83
T;T;.;T;.
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.074
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L;L;.;L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.57
N;N;N;N;N
REVEL
Benign
0.022
Sift
Benign
0.054
T;T;T;T;T
Sift4G
Benign
0.20
T;T;T;T;T
Polyphen
0.0040, 0.57
.;B;P;.;B
Vest4
0.25
MutPred
0.19
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.12
MPC
0.24
ClinPred
0.048
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs574055101; hg19: chr2-232879665; API