Genetic Variant NM_001257281.2:c.1582-78C>G (chr2-232343267-C-G) – 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.1582-78C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 1,259,900 control chromosomes in the GnomAD database, including 5,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2212 hom., cov: 33)

Exomes 𝑓: 0.069 ( 3627 hom. )

Consequence

DIS3L2
NM_001257281.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.59

Publications

2 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=-0.75).

BP6

Variant 2-232343267-C-G is Benign according to our data. Variant chr2-232343267-C-G is described in ClinVar as Benign. ClinVar VariationId is 1296810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.1582-78C>G		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.1582-78C>G		intron	N/A	ENSP00000273009.6	Q8IYB7-3
	NRBF2P6	ENST00000513620.1	TSL:6	n.152C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20134

AN:

152078

Hom.:

2201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.0339

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0600

Gnomad OTH

AF:

0.121

GnomAD4 exome

AF:

0.0686

AC:

75934

AN:

1107704

Hom.:

3627

Cov.:

AF XY:

0.0670

AC XY:

36860

AN XY:

550440

show subpopulations

African (AFR)

AF:

0.306

AC:

7559

AN:

24714

American (AMR)

AF:

0.150

AC:

4146

AN:

27590

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

1438

AN:

19192

East Asian (EAS)

AF:

0.0310

AC:

1110

AN:

35864

South Asian (SAS)

AF:

0.0569

AC:

3616

AN:

63530

European-Finnish (FIN)

AF:

0.0541

AC:

2571

AN:

47496

Middle Eastern (MID)

AF:

0.0753

AC:

263

AN:

3492

European-Non Finnish (NFE)

AF:

0.0615

AC:

51511

AN:

838202

Other (OTH)

AF:

0.0781

AC:

3720

AN:

47624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3382

6765

10147

13530

16912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1994

3988

5982

7976

9970

<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:

0.133

AC:

20186

AN:

152196

Hom.:

2212

Cov.:

AF XY:

0.130

AC XY:

9683

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.303

AC:

12585

AN:

41504

American (AMR)

AF:

0.121

AC:

1848

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0767

AC:

266

AN:

3468

East Asian (EAS)

AF:

0.0332

AC:

172

AN:

5174

South Asian (SAS)

AF:

0.0539

AC:

260

AN:

4824

European-Finnish (FIN)

AF:

0.0574

AC:

609

AN:

10608

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0600

AC:

4079

AN:

68014

Other (OTH)

AF:

0.124

AC:

262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

825

1649

2474

3298

4123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0280

Hom.:

Bravo

AF:

0.146

Asia WGS

AF:

0.0810

AC:

283

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

-0.75

CADD

Benign

1.9

(source)

DANN

Benign

0.27

PhyloP100

2.6

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