rs536336554

Variant names:

• chr1-93876326-C-T
• rs536336554
• NM_014597.5:c.1609G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014597.5(DNTTIP2):​c.1609G>A​(p.Glu537Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,552,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: DNTTIP2 NM_014597.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015169889).

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.1609G>A	p.Glu537Lys	missense	Exon 2 of 7	NP_055412.2	Q5QJE6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNTTIP2	ENST00000436063.7	TSL:1 MANE Select	c.1609G>A	p.Glu537Lys	missense	Exon 2 of 7	ENSP00000411010.2	Q5QJE6
	DNTTIP2	ENST00000359208.6	TSL:2	n.1609G>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000352137.6	J3KP30
	DNTTIP2	ENST00000460191.1	TSL:2	n.2908G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151908 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000379 AC: 6 AN: 158146 AF XY: 0.0000360

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 28 AN: 1400270 Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 19 AN XY: 690916

African (AFR) AF: 0.00 AC: 0 AN: 31514

American (AMR) AF: 0.00 AC: 0 AN: 35570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35782

South Asian (SAS) AF: 0.000302 AC: 24 AN: 79430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1079344

Other (OTH) AF: 0.0000172 AC: 1 AN: 58090

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152026 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000201 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.22
DANN	Benign	0.37
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.12
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.067
Sift	Benign	0.53	T
Sift4G	Benign	0.82	T
Polyphen		0.032	B
Vest4		0.074
MVP		0.12
MPC		0.070
ClinPred		0.017	T
GERP RS		-6.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.069
gMVP		0.059
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs536336554; hg19: chr1-94341882;