2-232334711-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152383.5(DIS3L2):c.2370C>T(p.Gly790Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,608,166 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 8 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00500

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 2-232334711-C-T is Benign according to our data. Variant chr2-232334711-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232334711-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00232 (354/152348) while in subpopulation NFE AF= 0.00388 (264/68030). AF 95% confidence interval is 0.0035. There are 0 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5 link	c.2370C>T	p.Gly790Gly	synonymous_variant	Exon 19 of 21	ENST00000325385.12	NP_689596.4	Q8IYB7-1
DIS3L2	NM_001257281.2 link	c.1582-8634C>T		intron_variant	Intron 13 of 13		NP_001244210.1	Q8IYB7-3
DIS3L2	NR_046476.2 link	n.2443C>T		non_coding_transcript_exon_variant	Exon 19 of 21
DIS3L2	NR_046477.2 link	n.2422C>T		non_coding_transcript_exon_variant	Exon 18 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 link	c.2370C>T	p.Gly790Gly	synonymous_variant	Exon 19 of 21	5	NM_152383.5	ENSP00000315569.7		Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

354

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00280

AC:

669

AN:

238674

Hom.:

AF XY:

0.00284

AC XY:

369

AN XY:

129906

show subpopulations

Gnomad AFR exome

AF:

0.000891

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.000346

Gnomad SAS exome

AF:

0.000778

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00469

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00433

AC:

6301

AN:

1455818

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

3052

AN XY:

723868

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00256

Gnomad4 NFE exome

AF:

0.00520

Gnomad4 OTH exome

AF:

0.00314

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152348

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00254

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Perlman syndrome

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jan 07, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DIS3L2: BP4, BP7 -

Apr 19, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 19, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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