Genetic Variant DIS3L2:c.1582-193C>T (chr2-232343152-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001257281.2(DIS3L2):c.1582-193C>T variant causes a intron change. The variant allele was found at a frequency of 0.0749 in 616,354 control chromosomes in the GnomAD database, including 2,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1036 hom., cov: 33)

Exomes 𝑓: 0.067 ( 1334 hom. )

Consequence

DIS3L2
NM_001257281.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.59

Publications

1 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 links:

NRBF2P6 (HGNC:54797): (NRBF2 pseudogene 6)

NRBF2P6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-232343152-C-T is Benign according to our data. Variant chr2-232343152-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257281.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_001257281.2		c.1582-193C>T		intron	N/A	NP_001244210.1	Q8IYB7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000273009.10	TSL:2	c.1582-193C>T		intron	N/A	ENSP00000273009.6	Q8IYB7-3
	NRBF2P6	ENST00000513620.1	TSL:6	n.37C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15273

AN:

152176

Hom.:

1033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0769

Gnomad EAS

AF:

0.0342

Gnomad SAS

AF:

0.0529

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0974

GnomAD4 exome

AF:

0.0665

AC:

30880

AN:

464060

Hom.:

1334

Cov.:

AF XY:

0.0642

AC XY:

15755

AN XY:

245514

show subpopulations

African (AFR)

AF:

0.188

AC:

2341

AN:

12432

American (AMR)

AF:

0.145

AC:

3201

AN:

22028

Ashkenazi Jewish (ASJ)

AF:

0.0777

AC:

1040

AN:

13382

East Asian (EAS)

AF:

0.0315

AC:

969

AN:

30764

South Asian (SAS)

AF:

0.0564

AC:

2518

AN:

44676

European-Finnish (FIN)

AF:

0.0549

AC:

2160

AN:

39376

Middle Eastern (MID)

AF:

0.0664

AC:

122

AN:

1836

European-Non Finnish (NFE)

AF:

0.0607

AC:

16644

AN:

274084

Other (OTH)

AF:

0.0740

AC:

1885

AN:

25482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1275

2550

3824

5099

6374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<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:

0.100

AC:

15298

AN:

152294

Hom.:

1036

Cov.:

AF XY:

0.0986

AC XY:

7339

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.191

AC:

7944

AN:

41538

American (AMR)

AF:

0.110

AC:

1677

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

267

AN:

3472

East Asian (EAS)

AF:

0.0335

AC:

174

AN:

5188

South Asian (SAS)

AF:

0.0532

AC:

257

AN:

4832

European-Finnish (FIN)

AF:

0.0572

AC:

608

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0596

AC:

4053

AN:

68022

Other (OTH)

AF:

0.101

AC:

214

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

688

1377

2065

2754

3442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0655

Hom.:

218

Bravo

AF:

0.110

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.4

(source)

DANN

Benign

0.85

PhyloP100

3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over