Variant 9-34343402-CAAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_001161.5(NUDT2):c.410_412delAAG(p.Glu137del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000412 in 1,456,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NUDT2
NM_001161.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 3.72

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001161.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT2	NM_001161.5 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	5/5	ENST00000379158.7	NP_001152.1	P50583
NUDT2	NM_001244390.2 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	3/3		NP_001231319.1	P50583
NUDT2	NM_147172.3 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	5/5		NP_671701.1	P50583
NUDT2	NM_147173.3 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	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.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	5/5	3	NM_001161.5	ENSP00000368455.1	P50583
NUDT2	ENST00000346365.8 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	4/4	1		ENSP00000344187.4	P50583
NUDT2	ENST00000379155.9 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	5/5	3		ENSP00000368452.5	P50583
NUDT2	ENST00000618590.1 linkuse as main transcript	c.410_412delAAG	p.Glu137del	disruptive_inframe_deletion	3/3	3		ENSP00000482384.1	P50583

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247368

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133760

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:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456532

Hom.:

AF XY:

0.00000414

AC XY:

AN XY:

723832

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual developmental disorder with or without peripheral neuropathy

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	Dec 31, 2024	A homozygous three base pair deletion (c.410_412del) in exon 5 of the NUDT2 gene that results in deletion of amino acid glutamic acid at codon 137 was detected (p.Glu137del). This variant has not been reported in the 1000 genomes and has a MAF of 0.0004% in the gnomAD database. The in-silico prediction of the variant is damaging MutationTaster2. The reference region is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. -
Uncertain significance, no assertion criteria provided	research	Houlden Lab, UCL Institute of Neurology	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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