9-34343436-C-T

Position:

chr9-34343436-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001161.5(NUDT2):c.440C>T(p.Ala147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000884 in 1,582,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

NUDT2
NM_001161.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.641

Variant links:

Genes affected

NUDT2 (HGNC:8049): (nudix hydrolase 2) This gene encodes a member of the MutT family of nucleotide pyrophosphatases, a subset of the larger NUDIX hydrolase family. The gene product possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. The enzyme asymmetrically hydrolyzes Ap4A to yield AMP and ATP and is responsible for maintaining the intracellular level of the dinucleotide Ap4A, the function of which has yet to be established. This gene may be a candidate tumor suppressor gene. Alternative splicing has been observed at this locus and four transcript variants, all encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

NUDT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.053313106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT2	NM_001161.5 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	5/5	ENST00000379158.7	NP_001152.1	P50583
NUDT2	NM_001244390.2 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	3/3		NP_001231319.1	P50583
NUDT2	NM_147172.3 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	5/5		NP_671701.1	P50583
NUDT2	NM_147173.3 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	4/4		NP_671702.1	P50583

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUDT2	ENST00000379158.7 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	5/5	3	NM_001161.5	ENSP00000368455.1	P50583
NUDT2	ENST00000346365.8 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	4/4	1		ENSP00000344187.4	P50583
NUDT2	ENST00000379155.9 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	5/5	3		ENSP00000368452.5	P50583
NUDT2	ENST00000618590.1 linkuse as main transcript	c.440C>T	p.Ala147Val	missense_variant	3/3	3		ENSP00000482384.1	P50583

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000887

AC:

AN:

225550

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

121086

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:

0.00000976

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.00000769

AC:

AN:

1430884

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

707978

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:

0.00000913

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Sep 06, 2022

The c.440C>T (p.A147V) alteration is located in exon 5 (coding exon 2) of the NUDT2 gene. This alteration results from a C to T substitution at nucleotide position 440, causing the alanine (A) at amino acid position 147 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.49

.;.;T;.

M_CAP

Benign

0.0043

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.40

N;N;.;N

REVEL

Benign

0.12

Sift

Uncertain

0.018

D;D;.;D

Sift4G

Uncertain

0.059

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.067

MutPred

0.53

Loss of disorder (P = 0.0738);Loss of disorder (P = 0.0738);Loss of disorder (P = 0.0738);Loss of disorder (P = 0.0738);

MVP

0.030

MPC

1.3

ClinPred

0.30

GERP RS

4.5

Varity_R

0.11

gMVP

0.53

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