chr9-34342932-G-A

Position:

• chr9-34342932-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001161.5(NUDT2):​c.128-192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,004 control chromosomes in the GnomAD database, including 1,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1496 hom., cov: 31)
• Consequence: NUDT2 NM_001161.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 9-34342932-G-A is Benign according to our data. Variant chr9-34342932-G-A is described in ClinVar as [Benign]. Clinvar id is 1240957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT2	NM_001161.5	c.128-192G>A		intron_variant		ENST00000379158.7
NUDT2	NM_001244390.2	c.128-192G>A		intron_variant
NUDT2	NM_147172.3	c.128-192G>A		intron_variant
NUDT2	NM_147173.3	c.128-192G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT2	ENST00000379158.7	c.128-192G>A		intron_variant		3	NM_001161.5	P1
NUDT2	ENST00000346365.8	c.128-192G>A		intron_variant		1		P1
NUDT2	ENST00000379155.9	c.128-192G>A		intron_variant		3		P1
NUDT2	ENST00000618590.1	c.128-192G>A		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18654 AN: 151886 Hom.: 1496 Cov.: 31

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00542

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18643 AN: 152004 Hom.: 1496 Cov.: 31 AF XY: 0.119 AC XY: 8861 AN XY: 74262

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00524

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.124

Alfa AF: 0.144 Hom.: 226

Bravo AF: 0.115

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.33

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: rs10972068; hg19: chr9-34342930; COSMIC: COSV60678409;