2-232014961-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152383.5(DIS3L2):c.34C>T(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,613,506 control chromosomes in the GnomAD database, including 2,550 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.080 ( 958 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1592 hom. )

Consequence

DIS3L2
NM_152383.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.275

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]

DIS3L2 links:

ENSG00000227033 (HGNC:):

ENSG00000227033 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.520054E-4).

BP6

Variant 2-232014961-C-T is Benign according to our data. Variant chr2-232014961-C-T is described in ClinVar as [Benign]. Clinvar id is 334928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232014961-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5 link	c.34C>T	p.Pro12Ser	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
DIS3L2	ENST00000325385.12 link	c.34C>T	p.Pro12Ser	missense_variant	Exon 2 of 21	5	NM_152383.5	ENSP00000315569.7		Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.0799

AC:

12145

AN:

152056

Hom.:

957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0487

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0548

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0303

Gnomad OTH

AF:

0.0579

GnomAD3 exomes

AF:

0.0450

AC:

11214

AN:

248948

Hom.:

518

AF XY:

0.0430

AC XY:

5803

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.0449

Gnomad ASJ exome

AF:

0.0472

Gnomad EAS exome

AF:

0.00162

Gnomad SAS exome

AF:

0.0540

Gnomad FIN exome

AF:

0.0373

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.0343

AC:

50120

AN:

1461332

Hom.:

1592

Cov.:

AF XY:

0.0345

AC XY:

25097

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.0488

Gnomad4 EAS exome

AF:

0.000932

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.0362

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0434

GnomAD4 genome

AF:

0.0798

AC:

12148

AN:

152174

Hom.:

958

Cov.:

AF XY:

0.0783

AC XY:

5826

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0486

Gnomad4 ASJ

AF:

0.0481

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0341

Gnomad4 NFE

AF:

0.0303

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0345

Hom.:

375

Bravo

AF:

0.0861

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0283

AC:

109

ESP6500AA

AF:

0.197

AC:

726

ESP6500EA

AF:

0.0290

AC:

237

ExAC

AF:

0.0481

AC:

5806

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

EpiCase

AF:

0.0272

EpiControl

AF:

0.0267

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Perlman syndrome

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.96

DANN

Benign

0.51

DEOGEN2

Benign

0.0026

.;T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.70

T;T;.;T;.

MetaRNN

Benign

0.00095

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

L;L;L;.;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.030

N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.27

T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.0

.;B;B;.;B

Vest4

0.031

MPC

0.22

ClinPred

0.00075

GERP RS

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over