chr9-34343339-C-T

Variant names:

Variant summary

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

The NM_001161.5(NUDT2):c.343C>T(p.Arg115Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000161 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

NUDT2
NM_001161.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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=0.015935302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT2	NM_001161.5 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 5	ENST00000379158.7	NP_001152.1	P50583
NUDT2	NM_001244390.2 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 3 of 3		NP_001231319.1	P50583
NUDT2	NM_147172.3 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 5		NP_671701.1	P50583
NUDT2	NM_147173.3 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 4 of 4		NP_671702.1	P50583

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUDT2	ENST00000379158.7 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 5	3	NM_001161.5	ENSP00000368455.1	P50583
NUDT2	ENST00000346365.8 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 4 of 4	1		ENSP00000344187.4	P50583
NUDT2	ENST00000379155.9 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 5	3		ENSP00000368452.5	P50583
NUDT2	ENST00000618590.1 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 3 of 3	3		ENSP00000482384.1	P50583

Frequencies

GnomAD3 genomes

AF:

0.000763

AC:

116

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000228

AC:

AN:

250412

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00300

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461580

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152224

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000327

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 22, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

.;.;D;.

M_CAP

Benign

0.037

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;M

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.6

D;D;.;D

REVEL

Benign

0.24

Sift

Benign

0.049

D;D;.;D

Sift4G

Benign

0.079

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.22

MVP

0.24

MPC

0.80

ClinPred

0.13

GERP RS

5.0

Varity_R

0.70

gMVP

0.74

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