2-232333889-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152383.5(DIS3L2):​c.2060G>T​(p.Arg687Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DIS3L2
NM_152383.5 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DIS3L2NM_152383.5 linkc.2060G>T p.Arg687Leu missense_variant Exon 17 of 21 ENST00000325385.12 NP_689596.4 Q8IYB7-1
DIS3L2NM_001257281.2 linkc.1582-9456G>T intron_variant Intron 13 of 13 NP_001244210.1 Q8IYB7-3
DIS3L2NR_046476.2 linkn.2133G>T non_coding_transcript_exon_variant Exon 17 of 21
DIS3L2NR_046477.2 linkn.2112G>T non_coding_transcript_exon_variant Exon 16 of 19

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DIS3L2ENST00000325385.12 linkc.2060G>T p.Arg687Leu missense_variant Exon 17 of 21 5 NM_152383.5 ENSP00000315569.7 Q8IYB7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460542
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726632
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.45
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;.;D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.50
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;.
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Benign
0.18
Sift
Benign
0.046
D;D;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.087
B;B;.
Vest4
0.60
MutPred
0.79
Loss of catalytic residue at R687 (P = 0.1291);Loss of catalytic residue at R687 (P = 0.1291);.;
MVP
0.13
MPC
0.56
ClinPred
0.96
D
GERP RS
2.5
Varity_R
0.27
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-233198599; API