Genetic Variant DNTTIP2:p.Arg633His (chr1-93873123-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014597.5(DNTTIP2):c.1898G>A(p.Arg633His) variant causes a missense change. The variant allele was found at a frequency of 0.000922 in 1,603,292 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

DNTTIP2
NM_014597.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Publications

6 publications found

Variant links:

Genes affected

DNTTIP2 (HGNC:24013): (deoxynucleotidyltransferase terminal interacting protein 2) This gene is thought to be involved in chromatin remodeling and gene transcription. The encoded nuclear protein binds to and enhances the transcriptional activity of the estrogen receptor alpha, and also interacts with terminal deoxynucleotidyltransferase. The expression profile of this gene is a potential biomarker for chronic obstructive pulmonary disease. [provided by RefSeq, Dec 2010]

DNTTIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06584659).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014597.5. 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
	DNTTIP2	NM_014597.5	MANE Select	c.1898G>A	p.Arg633His	missense	Exon 4 of 7	NP_055412.2	Q5QJE6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNTTIP2	ENST00000436063.7	TSL:1 MANE Select	c.1898G>A	p.Arg633His	missense	Exon 4 of 7	ENSP00000411010.2	Q5QJE6
DNTTIP2	ENST00000359208.6	TSL:2	n.1759G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000352137.6	J3KP30
DNTTIP2	ENST00000496535.6	TSL:2	n.247G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000986

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000731

AC:

180

AN:

246144

AF XY:

0.000749

show subpopulations

Gnomad AFR exome

AF:

0.000260

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000847

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000957

AC:

1389

AN:

1451208

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

640

AN XY:

722252

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33060

American (AMR)

AF:

0.00107

AC:

AN:

43948

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25936

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39388

South Asian (SAS)

AF:

0.00101

AC:

AN:

85306

European-Finnish (FIN)

AF:

0.000132

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00109

AC:

1202

AN:

1104762

Other (OTH)

AF:

0.000601

AC:

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.000592

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41530

American (AMR)

AF:

0.000262

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000950

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000986

AC:

AN:

67976

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000937

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000856

AC:

ExAC

AF:

0.000729

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00136

EpiControl

AF:

0.000653

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.86

M_CAP

Benign

0.018

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.8

PhyloP100

4.0

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.16

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.53

MVP

0.45

MPC

0.38

ClinPred

0.10

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.16

Mutation Taster

=68/32

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

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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