1-93876596-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014597.5(DNTTIP2):​c.1339A>G​(p.Ser447Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DNTTIP2
NM_014597.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31545168).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNTTIP2NM_014597.5 linkuse as main transcriptc.1339A>G p.Ser447Gly missense_variant 2/7 ENST00000436063.7 NP_055412.2 Q5QJE6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNTTIP2ENST00000436063.7 linkuse as main transcriptc.1339A>G p.Ser447Gly missense_variant 2/71 NM_014597.5 ENSP00000411010.2 Q5QJE6
DNTTIP2ENST00000359208.6 linkuse as main transcriptn.1339A>G non_coding_transcript_exon_variant 2/62 ENSP00000352137.6 J3KP30
DNTTIP2ENST00000460191.1 linkuse as main transcriptn.2638A>G non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsSep 03, 2024The c.1339A>G (p.S447G) alteration is located in exon 2 (coding exon 2) of the DNTTIP2 gene. This alteration results from a A to G substitution at nucleotide position 1339, causing the serine (S) at amino acid position 447 to be replaced by a glycine (G). 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
0.21
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.076
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.035
D
Polyphen
1.0
D
Vest4
0.30
MutPred
0.15
Loss of phosphorylation at S447 (P = 0.0189);
MVP
0.75
MPC
0.38
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.43
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.

Other links and lift over

dbSNP: rs1656012042; hg19: chr1-94342152; API