9-34338895-C-G

Position:

• chr9-34338895-C-G

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.-17+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 731,820 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (32 hom.)
• Consequence: NUDT2 NM_001161.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570

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=-0.57).
• BP6: Variant 9-34338895-C-G is Benign according to our data. Variant chr9-34338895-C-G is described in ClinVar as [Benign]. Clinvar id is 1229661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT2	NM_001161.5	c.-17+48C>G		intron_variant		ENST00000379158.7
NUDT2	NM_001244390.2	c.-16-129C>G		intron_variant
NUDT2	NM_147172.3	c.-17+48C>G		intron_variant
NUDT2	NM_147173.3	c.-17+48C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT2	ENST00000379158.7	c.-17+48C>G		intron_variant		3	NM_001161.5	P1
NUDT2	ENST00000346365.8	c.-17+48C>G		intron_variant		1		P1
NUDT2	ENST00000379155.9	c.-17+48C>G		intron_variant		3		P1
NUDT2	ENST00000618590.1	c.-16-129C>G		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2510 AN: 152152 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00210 AC: 1219 AN: 579550 Hom.: 32 Cov.: 8 AF XY: 0.00171 AC XY: 512 AN XY: 299426

Gnomad4 AFR exome AF: 0.0563

Gnomad4 AMR exome AF: 0.00463

Gnomad4 ASJ exome AF: 0.0000721

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.00434

GnomAD4 genome AF: 0.0165 AC: 2510 AN: 152270 Hom.: 72 Cov.: 32 AF XY: 0.0163 AC XY: 1212 AN XY: 74460

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0158 Hom.: 4

Bravo AF: 0.0190

Asia WGS AF: 0.00144 AC: 5 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	-0.57
CADD	Benign	14
DANN	Benign	0.88

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: rs116357346; hg19: chr9-34338893;