2-232300055-A-G

Variant summary

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

The NM_152383.5(DIS3L2):​c.1675A>G​(p.Thr559Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DIS3L2
NM_152383.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25006112).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DIS3L2NM_152383.5 linkc.1675A>G p.Thr559Ala missense_variant Exon 14 of 21 ENST00000325385.12 NP_689596.4 Q8IYB7-1
DIS3L2NM_001257281.2 linkc.1581+36693A>G intron_variant Intron 13 of 13 NP_001244210.1 Q8IYB7-3
DIS3L2NR_046476.2 linkn.1821A>G non_coding_transcript_exon_variant Exon 14 of 21
DIS3L2NR_046477.2 linkn.1797A>G non_coding_transcript_exon_variant Exon 13 of 19

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DIS3L2ENST00000325385.12 linkc.1675A>G p.Thr559Ala missense_variant Exon 14 of 21 5 NM_152383.5 ENSP00000315569.7 Q8IYB7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461396
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726950
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.066
T;T;T
Eigen
Benign
0.040
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
T;.;D
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L;.
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.082
B;B;.
Vest4
0.33
MutPred
0.46
Loss of stability (P = 0.0822);Loss of stability (P = 0.0822);.;
MVP
0.10
MPC
0.68
ClinPred
0.81
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.47

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: chr2-233164765; API