chr1-93876743-C-T

Position:

• chr1-93876743-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014597.5(DNTTIP2):​c.1192G>A​(p.Asp398Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: DNTTIP2 NM_014597.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.185

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04756233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTTIP2	NM_014597.5	c.1192G>A	p.Asp398Asn	missense_variant	2/7	ENST00000436063.7	NP_055412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNTTIP2	ENST00000436063.7	c.1192G>A	p.Asp398Asn	missense_variant	2/7	1	NM_014597.5	ENSP00000411010.2
DNTTIP2	ENST00000359208.6	n.1192G>A		non_coding_transcript_exon_variant	2/6	2		ENSP00000352137.6
DNTTIP2	ENST00000460191.1	n.2491G>A		non_coding_transcript_exon_variant	2/3	2
DNTTIP2	ENST00000496672.1	n.*16G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1192G>A (p.D398N) alteration is located in exon 2 (coding exon 2) of the DNTTIP2 gene. This alteration results from a G to A substitution at nucleotide position 1192, causing the aspartic acid (D) at amino acid position 398 to be replaced by an asparagine (N). 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	0.072
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.056
Sift	Benign	0.25	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.13		Gain of glycosylation at S397 (P = 0.1277);
MVP		0.17
MPC		0.063
ClinPred		0.043	T
GERP RS		1.2
Varity_R		0.19
gMVP		0.044

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-94342299;