dbSNP rs6711186: DIS3L2:c.*249T>C (chr2-232343824-T-C) – 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.*249T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 420,556 control chromosomes in the GnomAD database, including 24,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14252 hom., cov: 33)

Exomes 𝑓: 0.23 ( 10176 hom. )

Consequence

DIS3L2
NM_001257281.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.80

Publications

3 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=-0.77).

BP6

Variant 2-232343824-T-C is Benign according to our data. Variant chr2-232343824-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 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.*249T>C		3_prime_UTR	Exon 14 of 14	NP_001244210.1	Q8IYB7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000273009.10	TSL:2	c.*249T>C		3_prime_UTR	Exon 14 of 14	ENSP00000273009.6	Q8IYB7-3
	NRBF2P6	ENST00000513620.1	TSL:6	n.709T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53635

AN:

152004

Hom.:

14205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.229

AC:

61596

AN:

268434

Hom.:

10176

Cov.:

AF XY:

0.222

AC XY:

30910

AN XY:

139276

show subpopulations

African (AFR)

AF:

0.734

AC:

5944

AN:

8100

American (AMR)

AF:

0.490

AC:

5716

AN:

11674

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

1554

AN:

8692

East Asian (EAS)

AF:

0.527

AC:

10067

AN:

19100

South Asian (SAS)

AF:

0.195

AC:

4040

AN:

20668

European-Finnish (FIN)

AF:

0.191

AC:

4439

AN:

23200

Middle Eastern (MID)

AF:

0.199

AC:

518

AN:

2600

European-Non Finnish (NFE)

AF:

0.160

AC:

25370

AN:

158512

Other (OTH)

AF:

0.248

AC:

3948

AN:

15888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1963

3926

5890

7853

9816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.353

AC:

53749

AN:

152122

Hom.:

14252

Cov.:

AF XY:

0.353

AC XY:

26247

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.729

AC:

30241

AN:

41476

American (AMR)

AF:

0.387

AC:

5912

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

599

AN:

3470

East Asian (EAS)

AF:

0.497

AC:

2565

AN:

5166

South Asian (SAS)

AF:

0.200

AC:

965

AN:

4822

European-Finnish (FIN)

AF:

0.170

AC:

1805

AN:

10600

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.159

AC:

10787

AN:

68002

Other (OTH)

AF:

0.312

AC:

659

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1299

2599

3898

5198

6497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.276

Hom.:

1244

Bravo

AF:

0.391

Asia WGS

AF:

0.364

AC:

1265

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

-0.77

CADD

Benign

1.6

(source)

DANN

Benign

0.56

PhyloP100

2.8

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