dbSNP rs753517918: DNASE1L2:p.Pro156Thr (chr16-2237524-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001374.3(DNASE1L2):c.466C>A(p.Pro156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P156S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNASE1L2
NM_001374.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.30

Publications

0 publications found

Variant links:

Genes affected

DNASE1L2 (HGNC:2958): (deoxyribonuclease 1 like 2) Predicted to enable DNA binding activity and deoxyribonuclease I activity. Predicted to be involved in DNA catabolic process, endonucleolytic. Predicted to act upstream of or within corneocyte development and hair follicle development. Predicted to be located in cytoplasm and extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNASE1L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07850155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374.3. 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
	DNASE1L2	NM_001374.3	MANE Select	c.466C>A	p.Pro156Thr	missense	Exon 5 of 7	NP_001365.1	Q92874-1
	DNASE1L2	NM_001301680.2		c.466C>A	p.Pro156Thr	missense	Exon 5 of 7	NP_001288609.1	Q92874-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNASE1L2	ENST00000320700.10	TSL:1 MANE Select	c.466C>A	p.Pro156Thr	missense	Exon 5 of 7	ENSP00000316938.5	Q92874-1
DNASE1L2	ENST00000564065.5	TSL:1	c.466C>A	p.Pro156Thr	missense	Exon 4 of 6	ENSP00000454562.1	Q92874-1
DNASE1L2	ENST00000567494.5	TSL:1	c.466C>A	p.Pro156Thr	missense	Exon 5 of 7	ENSP00000455358.1	Q92874-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000460

AC:

AN:

217256

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000822

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718182

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33148

American (AMR)

AF:

0.00

AC:

AN:

43476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25790

East Asian (EAS)

AF:

0.00

AC:

AN:

38856

South Asian (SAS)

AF:

0.00

AC:

AN:

84154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105474

Other (OTH)

AF:

0.00

AC:

AN:

59784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.21

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.28

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.36

M_CAP

Benign

0.011

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-2.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.51

REVEL

Benign

0.0060

Sift

Benign

0.12

Sift4G

Benign

0.24

Polyphen

0.19

Vest4

0.19

MutPred

0.35

Gain of phosphorylation at P156 (P = 0.0277)

MVP

0.061

MPC

0.27

ClinPred

0.029

GERP RS

-1.8

Varity_R

0.042

gMVP

0.61

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over