dbSNP rs3754274: DNASE2B:p.Arg51Lys (chr1-84401927-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021233.3(DNASE2B):c.152G>A(p.Arg51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,530,442 control chromosomes in the GnomAD database, including 61,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4391 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57091 hom. )

Consequence

DNASE2B
NM_021233.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.172

Publications

24 publications found

Variant links:

Genes affected

DNASE2B (HGNC:28875): (deoxyribonuclease 2 beta) The protein encoded by this gene shares considerable sequence similarity to, and is structurally related to DNase II. The latter is a well characterized endonuclease that catalyzes DNA hydrolysis in the absence of divalent cations at acidic pH. Unlike DNase II which is ubiquitously expressed, expression of this gene product is restricted to the salivary gland and lungs. The gene has been localized to chromosome 1p22.3 adjacent (and in opposite orientation) to the uricase pseudogene. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DNASE2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.4982305E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE2B	NM_021233.3 link	c.152G>A	p.Arg51Lys	missense_variant	Exon 2 of 6	ENST00000370665.4	NP_067056.2	Q8WZ79-1Q66K39
DNASE2B	XM_047426625.1 link	c.-86G>A		5_prime_UTR_variant	Exon 1 of 5		XP_047282581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4 link	c.152G>A	p.Arg51Lys	missense_variant	Exon 2 of 6	1	NM_021233.3	ENSP00000359699.3		Q8WZ79-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33933

AN:

151950

Hom.:

4389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.252

AC:

38742

AN:

153456

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.0703

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.283

AC:

389838

AN:

1378374

Hom.:

57091

Cov.:

AF XY:

0.281

AC XY:

191084

AN XY:

681144

show subpopulations

African (AFR)

AF:

0.0672

AC:

1987

AN:

29566

American (AMR)

AF:

0.234

AC:

5859

AN:

25038

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

4769

AN:

23262

East Asian (EAS)

AF:

0.383

AC:

14092

AN:

36746

South Asian (SAS)

AF:

0.220

AC:

16153

AN:

73286

European-Finnish (FIN)

AF:

0.241

AC:

12305

AN:

51082

Middle Eastern (MID)

AF:

0.156

AC:

873

AN:

5580

European-Non Finnish (NFE)

AF:

0.296

AC:

318245

AN:

1076558

Other (OTH)

AF:

0.272

AC:

15555

AN:

57256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

12399

24798

37197

49596

61995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.223

AC:

33935

AN:

152068

Hom.:

4391

Cov.:

AF XY:

0.220

AC XY:

16385

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0787

AC:

3264

AN:

41498

American (AMR)

AF:

0.239

AC:

3657

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3468

East Asian (EAS)

AF:

0.377

AC:

1946

AN:

5158

South Asian (SAS)

AF:

0.234

AC:

1125

AN:

4812

European-Finnish (FIN)

AF:

0.221

AC:

2332

AN:

10558

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20079

AN:

67984

Other (OTH)

AF:

0.237

AC:

501

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1276

2552

3829

5105

6381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.258

Hom.:

11200

Bravo

AF:

0.217

ESP6500AA

AF:

0.0738

AC:

272

ESP6500EA

AF:

0.281

AC:

2296

ExAC

AF:

0.221

AC:

26162

Asia WGS

AF:

0.324

AC:

1125

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.011

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.32

MetaRNN

Benign

0.00055

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

0.17

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.35

REVEL

Benign

0.058

Sift

Benign

0.49

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.027

MPC

0.076

ClinPred

0.00057

GERP RS

-0.37

Varity_R

0.076

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3754274

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over