dbSNP rs759428794: DNASE2B:p.Asp244Ala (chr1-84412532-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021233.3(DNASE2B):c.731A>C(p.Asp244Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D244V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNASE2B
NM_021233.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.259

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051573336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE2B	NM_021233.3 link	c.731A>C	p.Asp244Ala	missense_variant	Exon 5 of 6	ENST00000370665.4	NP_067056.2	Q8WZ79-1Q66K39
DNASE2B	NM_058248.2 link	c.107A>C	p.Asp36Ala	missense_variant	Exon 3 of 4		NP_490649.1	Q8WZ79-2
DNASE2B	XM_047426625.1 link	c.494A>C	p.Asp165Ala	missense_variant	Exon 4 of 5		XP_047282581.1
DNASE2B	XM_011541878.3 link	c.107A>C	p.Asp36Ala	missense_variant	Exon 2 of 3		XP_011540180.1	Q8WZ79-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4 link	c.731A>C	p.Asp244Ala	missense_variant	Exon 5 of 6	1	NM_021233.3	ENSP00000359699.3		Q8WZ79-1
DNASE2B	ENST00000370662.3 link	c.107A>C	p.Asp36Ala	missense_variant	Exon 3 of 4	1		ENSP00000359696.3		Q8WZ79-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458284

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.034

Sift

Benign

0.88

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.086

B;.

Vest4

0.097

MutPred

0.36

Loss of sheet (P = 0.0817);.;

MVP

0.27

MPC

0.092

ClinPred

0.055

GERP RS

-5.2

Varity_R

0.059

gMVP

0.34

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over