Genetic Variant DIS3L2:c.1660-9184T>C (chr2-232290856-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_152383.5(DIS3L2):c.1660-9184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,072 control chromosomes in the GnomAD database, including 9,662 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9662 hom., cov: 32)

Consequence

DIS3L2
NM_152383.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P

DIS3L2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_152383.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DIS3L2	NM_152383.5	MANE Select	c.1660-9184T>C	intron	N/A	NP_689596.4
DIS3L2	NM_001257281.2		c.1581+27494T>C	intron	N/A	NP_001244210.1	Q8IYB7-3
DIS3L2	NR_046476.2		n.1806-9184T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.1660-9184T>C	intron	N/A	ENSP00000315569.7	Q8IYB7-1
DIS3L2	ENST00000390005.9	TSL:1	n.1660-9184T>C	intron	N/A	ENSP00000374655.5	Q8IYB7-2
DIS3L2	ENST00000445090.5	TSL:1	n.*886-9184T>C	intron	N/A	ENSP00000388999.1	Q8IYB7-4

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49630

AN:

151954

Hom.:

9634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.327

AC:

49715

AN:

152072

Hom.:

9662

Cov.:

AF XY:

0.326

AC XY:

24234

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.517

AC:

21434

AN:

41432

American (AMR)

AF:

0.393

AC:

6010

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

991

AN:

3472

East Asian (EAS)

AF:

0.498

AC:

2572

AN:

5166

South Asian (SAS)

AF:

0.251

AC:

1209

AN:

4822

European-Finnish (FIN)

AF:

0.173

AC:

1834

AN:

10596

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14624

AN:

67982

Other (OTH)

AF:

0.329

AC:

693

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1590

3179

4769

6358

7948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.258

Hom.:

10285

Bravo

AF:

0.357

Asia WGS

AF:

0.348

AC:

1211

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

2.3

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over