9-34343210-A-G

Position:

• chr9-34343210-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001161.5(NUDT2):​c.214A>G​(p.Ile72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDT2 NM_001161.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07464719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT2	NM_001161.5	c.214A>G	p.Ile72Val	missense_variant	5/5	ENST00000379158.7	NP_001152.1
NUDT2	NM_001244390.2	c.214A>G	p.Ile72Val	missense_variant	3/3		NP_001231319.1
NUDT2	NM_147172.3	c.214A>G	p.Ile72Val	missense_variant	5/5		NP_671701.1
NUDT2	NM_147173.3	c.214A>G	p.Ile72Val	missense_variant	4/4		NP_671702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT2	ENST00000379158.7	c.214A>G	p.Ile72Val	missense_variant	5/5	3	NM_001161.5	ENSP00000368455.1
NUDT2	ENST00000346365.8	c.214A>G	p.Ile72Val	missense_variant	4/4	1		ENSP00000344187.4
NUDT2	ENST00000379155.9	c.214A>G	p.Ile72Val	missense_variant	5/5	3		ENSP00000368452.5
NUDT2	ENST00000618590.1	c.214A>G	p.Ile72Val	missense_variant	3/3	3		ENSP00000482384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.214A>G (p.I72V) alteration is located in exon 5 (coding exon 2) of the NUDT2 gene. This alteration results from a A to G substitution at nucleotide position 214, causing the isoleucine (I) at amino acid position 72 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	0.081
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.72
DEOGEN2	Benign	0.0074	T;T;T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	.;.;T;.
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.48	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.17	N;N;.;N
REVEL	Benign	0.063
Sift	Benign	0.49	T;T;.;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.021
MutPred		0.55		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.11
MPC		0.39
ClinPred		0.096	T
GERP RS		0.59
Varity_R		0.071
gMVP		0.37

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

Other links and lift over

dbSNP: rs1820238513; hg19: chr9-34343208;