Variant 9-34343285-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001161.5(NUDT2):c.289G>C(p.Glu97Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NUDT2
NM_001161.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.73

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NUDT2	NM_001161.5 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	5/5	ENST00000379158.7
NUDT2	NM_001244390.2 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	3/3
NUDT2	NM_147172.3 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	5/5
NUDT2	NM_147173.3 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NUDT2	ENST00000379158.7 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	5/5	3	NM_001161.5	P1
NUDT2	ENST00000346365.8 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	4/4	1		P1
NUDT2	ENST00000379155.9 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	5/5	3		P1
NUDT2	ENST00000618590.1 linkuse as main transcript	c.289G>C	p.Glu97Gln	missense_variant	3/3	3		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726240

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

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 submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.289G>C (p.E97Q) alteration is located in exon 5 (coding exon 2) of the NUDT2 gene. This alteration results from a G to C substitution at nucleotide position 289, causing the glutamic acid (E) at amino acid position 97 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.0

N;N;.;N

REVEL

Benign

0.25

Sift

Uncertain

0.018

D;D;.;D

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

0.73

P;P;P;P

Vest4

0.79

MutPred

0.61

Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);

MVP

0.53

MPC

1.4

ClinPred

0.98

GERP RS

5.0

Varity_R

0.46

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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