Variant 1-93872182-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014597.5(DNTTIP2):c.1957A>G(p.Met653Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,580 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNTTIP2
NM_014597.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.139

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103331596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTTIP2	NM_014597.5 link	c.1957A>G	p.Met653Val	missense_variant	5/7	ENST00000436063.7	NP_055412.2	Q5QJE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNTTIP2	ENST00000436063.7 link	c.1957A>G	p.Met653Val	missense_variant	5/7	1	NM_014597.5	ENSP00000411010.2	Q5QJE6
DNTTIP2	ENST00000359208.6 link	n.*12A>G		non_coding_transcript_exon_variant	4/6	2		ENSP00000352137.6	J3KP30
DNTTIP2	ENST00000496535.6 link	n.306A>G		non_coding_transcript_exon_variant	2/4	2
DNTTIP2	ENST00000359208.6 link	n.*12A>G		3_prime_UTR_variant	4/6	2		ENSP00000352137.6	J3KP30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249098

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727068

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jun 17, 2024

The c.1957A>G (p.M653V) alteration is located in exon 5 (coding exon 5) of the DNTTIP2 gene. This alteration results from a A to G substitution at nucleotide position 1957, causing the methionine (M) at amino acid position 653 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.023

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0080

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

REVEL

Benign

0.067

Sift

Uncertain

0.026

Sift4G

Uncertain

0.027

Polyphen

0.016

Vest4

0.24

MutPred

0.53

Loss of ubiquitination at K658 (P = 0.0578);

MVP

0.20

MPC

0.068

ClinPred

0.038

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.078

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