2-232336618-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_152383.5(DIS3L2):c.2646A>G(p.Ser882Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,603,266 control chromosomes in the GnomAD database, including 13,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S882S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.13 ( 1713 hom., cov: 32)

Exomes 𝑓: 0.10 ( 11368 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.256

Publications

15 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.027).

BP6

Variant 2-232336618-A-G is Benign according to our data. Variant chr2-232336618-A-G is described in ClinVar as [Benign]. Clinvar id is 262631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5 link	c.2646A>G	p.Ser882Ser	synonymous_variant	Exon 21 of 21	ENST00000325385.12	NP_689596.4	Q8IYB7-1
DIS3L2	NR_046476.2 link	n.2719A>G		non_coding_transcript_exon_variant	Exon 21 of 21
DIS3L2	NR_046477.2 link	n.3292A>G		non_coding_transcript_exon_variant	Exon 19 of 19
DIS3L2	NM_001257281.2 link	c.1582-6727A>G		intron_variant	Intron 13 of 13		NP_001244210.1	Q8IYB7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 link	c.2646A>G	p.Ser882Ser	synonymous_variant	Exon 21 of 21	5	NM_152383.5	ENSP00000315569.7		Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19115

AN:

151878

Hom.:

1700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.0842

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.0801

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0849

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.143

AC:

32887

AN:

230524

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.0835

Gnomad EAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.0873

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.101

AC:

146236

AN:

1451268

Hom.:

11368

Cov.:

AF XY:

0.0995

AC XY:

71861

AN XY:

721996

show subpopulations

African (AFR)

AF:

0.151

AC:

5032

AN:

33406

American (AMR)

AF:

0.248

AC:

10947

AN:

44128

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

2270

AN:

26064

East Asian (EAS)

AF:

0.481

AC:

19004

AN:

39510

South Asian (SAS)

AF:

0.0778

AC:

6656

AN:

85514

European-Finnish (FIN)

AF:

0.0896

AC:

4150

AN:

46310

Middle Eastern (MID)

AF:

0.113

AC:

639

AN:

5660

European-Non Finnish (NFE)

AF:

0.0815

AC:

90536

AN:

1110558

Other (OTH)

AF:

0.116

AC:

7002

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

8216

16432

24647

32863

41079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.126

AC:

19152

AN:

151998

Hom.:

1713

Cov.:

AF XY:

0.127

AC XY:

9437

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.153

AC:

6329

AN:

41454

American (AMR)

AF:

0.183

AC:

2792

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0842

AC:

292

AN:

3468

East Asian (EAS)

AF:

0.458

AC:

2345

AN:

5124

South Asian (SAS)

AF:

0.0789

AC:

380

AN:

4814

European-Finnish (FIN)

AF:

0.0801

AC:

848

AN:

10592

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0849

AC:

5769

AN:

67954

Other (OTH)

AF:

0.144

AC:

304

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

766

1532

2298

3064

3830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0955

Hom.:

1210

Bravo

AF:

0.140

Asia WGS

AF:

0.222

AC:

771

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Perlman syndrome

Benign:3

Jul 30, 2021

Genome-Nilou Lab

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 06, 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

-0.66

CADD

Benign

2.0

(source)

DANN

Benign

0.52

PhyloP100

-0.26

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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2-232336618-A-G

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