Variant 1-93873123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

DNTTIP2 (HGNC:):

DNTTIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTTIP2	NM_014597.5 linkuse as main transcript	c.1898G>A	p.Arg633His	missense_variant	4/7	ENST00000436063.7	NP_055412.2	Q5QJE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNTTIP2	ENST00000436063.7 linkuse as main transcript	c.1898G>A	p.Arg633His	missense_variant	4/7	1	NM_014597.5	ENSP00000411010.2	Q5QJE6
DNTTIP2	ENST00000359208.6 linkuse as main transcript	n.1759G>A		non_coding_transcript_exon_variant	3/6	2		ENSP00000352137.6	J3KP30
DNTTIP2	ENST00000496535.6 linkuse as main transcript	n.247G>A		non_coding_transcript_exon_variant	1/4	2

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

GnomAD3 exomes

AF:

0.000731

AC:

180

AN:

246144

Hom.:

AF XY:

0.000749

AC XY:

100

AN XY:

133496

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 SAS exome

AF:

0.00111

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

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000601

GnomAD4 genome

AF:

0.000592

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000950

Gnomad4 NFE

AF:

0.000986

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00102

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1898G>A (p.R633H) alteration is located in exon 4 (coding exon 4) of the DNTTIP2 gene. This alteration results from a G to A substitution at nucleotide position 1898, causing the arginine (R) at amino acid position 633 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over