rs17272089

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152383.5(DIS3L2):c.1170C>T(p.Leu390Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,548 control chromosomes in the GnomAD database, including 638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 39 hom., cov: 32)

Exomes 𝑓: 0.026 ( 599 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.681

Publications

7 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 (BayesDel_noAF=-0.34).

BP6

Variant 2-232210371-C-T is Benign according to our data. Variant chr2-232210371-C-T is described in ClinVar as Benign. ClinVar VariationId is 334936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.681 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0176 (2688/152304) while in subpopulation SAS AF = 0.0447 (215/4810). AF 95% confidence interval is 0.0398. There are 39 homozygotes in GnomAd4. There are 1252 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DIS3L2	NM_152383.5 link	c.1170C>T	p.Leu390Leu	synonymous_variant	Exon 10 of 21	ENST00000325385.12	NP_689596.4
DIS3L2	NM_001257281.2 link	c.1170C>T	p.Leu390Leu	synonymous_variant	Exon 10 of 14		NP_001244210.1
DIS3L2	NR_046476.2 link	n.1316C>T		non_coding_transcript_exon_variant	Exon 10 of 21
DIS3L2	NR_046477.2 link	n.1292C>T		non_coding_transcript_exon_variant	Exon 9 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 link	c.1170C>T	p.Leu390Leu	synonymous_variant	Exon 10 of 21	5	NM_152383.5	ENSP00000315569.7

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2687

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00475

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0440

Gnomad FIN

AF:

0.00886

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0215

AC:

5373

AN:

249530

AF XY:

0.0234

show subpopulations

Gnomad AFR exome

AF:

0.00452

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0290

Gnomad EAS exome

AF:

0.000222

Gnomad FIN exome

AF:

0.00988

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0243

GnomAD4 exome

AF:

0.0258

AC:

37725

AN:

1461244

Hom.:

599

Cov.:

AF XY:

0.0264

AC XY:

19169

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.00442

AC:

148

AN:

33470

American (AMR)

AF:

0.0143

AC:

640

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

743

AN:

26116

East Asian (EAS)

AF:

0.000101

AC:

AN:

39682

South Asian (SAS)

AF:

0.0401

AC:

3459

AN:

86246

European-Finnish (FIN)

AF:

0.00914

AC:

488

AN:

53376

Middle Eastern (MID)

AF:

0.0372

AC:

214

AN:

5760

European-Non Finnish (NFE)

AF:

0.0274

AC:

30508

AN:

1111520

Other (OTH)

AF:

0.0252

AC:

1521

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1857

3713

5570

7426

9283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1168

2336

3504

4672

5840

<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:

0.0176

AC:

2688

AN:

152304

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1252

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00474

AC:

197

AN:

41576

American (AMR)

AF:

0.0131

AC:

200

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.0447

AC:

215

AN:

4810

European-Finnish (FIN)

AF:

0.00886

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0264

AC:

1794

AN:

68032

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

133

266

400

533

666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0232

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0286

EpiControl

AF:

0.0270

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Perlman syndrome

Benign:2

Feb 03, 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

Mar 22, 2021

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.1

(source)

DANN

Benign

0.80

PhyloP100

-0.68

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