2-232087576-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152383.5(DIS3L2):c.456A>G(p.Gln152Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,613,826 control chromosomes in the GnomAD database, including 6,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1098 hom., cov: 31)

Exomes 𝑓: 0.079 ( 5346 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0330

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Perlman syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

DIS3L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-232087576-A-G is Benign according to our data. Variant chr2-232087576-A-G is described in ClinVar as Benign. ClinVar VariationId is 262632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.033 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5 link	c.456A>G	p.Gln152Gln	synonymous_variant	Exon 6 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.456A>G	p.Gln152Gln	synonymous_variant	Exon 6 of 21	5	NM_152383.5	ENSP00000315569.7		Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16473

AN:

151940

Hom.:

1094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.0370

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0700

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0708

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.0954

AC:

23805

AN:

249446

AF XY:

0.0915

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.0987

Gnomad EAS exome

AF:

0.0357

Gnomad FIN exome

AF:

0.0645

Gnomad NFE exome

AF:

0.0729

Gnomad OTH exome

AF:

0.0848

GnomAD4 exome

AF:

0.0790

AC:

115504

AN:

1461770

Hom.:

5346

Cov.:

AF XY:

0.0789

AC XY:

57387

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.194

AC:

6485

AN:

33476

American (AMR)

AF:

0.163

AC:

7282

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

2516

AN:

26136

East Asian (EAS)

AF:

0.0340

AC:

1348

AN:

39696

South Asian (SAS)

AF:

0.107

AC:

9226

AN:

86244

European-Finnish (FIN)

AF:

0.0685

AC:

3658

AN:

53416

Middle Eastern (MID)

AF:

0.0766

AC:

442

AN:

5768

European-Non Finnish (NFE)

AF:

0.0714

AC:

79411

AN:

1111928

Other (OTH)

AF:

0.0850

AC:

5136

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

5477

10954

16430

21907

27384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3118

6236

9354

12472

15590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.109

AC:

16499

AN:

152056

Hom.:

1098

Cov.:

AF XY:

0.107

AC XY:

7979

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.187

AC:

7752

AN:

41444

American (AMR)

AF:

0.114

AC:

1748

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

334

AN:

3470

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5182

South Asian (SAS)

AF:

0.106

AC:

512

AN:

4822

European-Finnish (FIN)

AF:

0.0700

AC:

741

AN:

10590

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0708

AC:

4815

AN:

67966

Other (OTH)

AF:

0.105

AC:

222

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

733

1466

2200

2933

3666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0894

Hom.:

566

Bravo

AF:

0.116

Asia WGS

AF:

0.100

AC:

348

AN:

3478

EpiCase

AF:

0.0697

EpiControl

AF:

0.0668

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 12, 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

Feb 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: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

-0.89

CADD

Benign

0.99

(source)

DANN

Benign

0.39

PhyloP100

0.033

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over