Variant 9-34343313-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001161.5(NUDT2):c.317G>C(p.Arg106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

NUDT2
NM_001161.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.59

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 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=0.04452017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NUDT2	NM_001161.5 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	5/5	ENST00000379158.7
NUDT2	NM_001244390.2 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	3/3
NUDT2	NM_147172.3 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	5/5
NUDT2	NM_147173.3 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NUDT2	ENST00000379158.7 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	5/5	3	NM_001161.5	P1
NUDT2	ENST00000346365.8 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	4/4	1		P1
NUDT2	ENST00000379155.9 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	5/5	3		P1
NUDT2	ENST00000618590.1 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	3/3	3		P1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

250738

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000694

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:

0.0000177

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459674

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000672

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:

0.0000162

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.0000758

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.078

T;T;T;T

Eigen

Benign

0.070

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.0059

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;L;L;L

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

N;N;.;N

REVEL

Benign

0.080

Sift

Benign

0.18

T;T;.;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.20

B;B;B;B

Vest4

0.29

MutPred

0.59

Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);Loss of solvent accessibility (P = 0.0404);

MVP

0.45

MPC

1.2

ClinPred

0.074

GERP RS

5.0

Varity_R

0.58

gMVP

0.84

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over