rs11788425

Variant names:

• chr9-34333857-A-G
• rs11788425
• NM_001161.5:c.-264-2372A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161.5(NUDT2):​c.-264-2372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,952 control chromosomes in the GnomAD database, including 10,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10785 hom., cov: 31)
• Consequence: NUDT2 NM_001161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 5 publications found

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]

KIF24 (HGNC:19916): (kinesin family member 24) This gene encodes a member of the kinesin superfamily of microtubule-based motor proteins which are involved in the intracellular transport of membranous organelles, protein complexes, and mRNAs. They also play critical roles in mitosis, morphogenesis, and signal transduction. The encoded protein contains an N-terminal sterile alpha motif (SAM) domain and an ATP-binding kinesin motor domain. It binds centriolar coiled coil protein 110 and centrosomal protein 97 and localizes to the mother centriole to regulate ciliogenesis by controlling microtubule polymerization. [provided by RefSeq, Mar 2017]

KIF24 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT2	NM_001161.5	c.-264-2372A>G		intron_variant	Intron 1 of 4	ENST00000379158.7	NP_001152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT2	ENST00000379158.7	c.-264-2372A>G		intron_variant	Intron 1 of 4	3	NM_001161.5	ENSP00000368455.1
NUDT2	ENST00000346365.9	c.-152+4258A>G		intron_variant	Intron 1 of 3	1		ENSP00000344187.4
NUDT2	ENST00000379155.9	c.-193-2443A>G		intron_variant	Intron 1 of 4	3		ENSP00000368452.5
NUDT2	ENST00000618590.1	c.-17+4258A>G		intron_variant	Intron 1 of 2	3		ENSP00000482384.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53234 AN: 151834 Hom.: 10780 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.350 AC: 53247 AN: 151952 Hom.: 10785 Cov.: 31 AF XY: 0.353 AC XY: 26202 AN XY: 74288

African (AFR) AF: 0.139 AC: 5778 AN: 41452

American (AMR) AF: 0.352 AC: 5376 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1701 AN: 5162

South Asian (SAS) AF: 0.575 AC: 2770 AN: 4816

European-Finnish (FIN) AF: 0.388 AC: 4091 AN: 10548

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30665 AN: 67942

Other (OTH) AF: 0.383 AC: 808 AN: 2108

Alfa AF: 0.417 Hom.: 42984

Bravo AF: 0.334

Asia WGS AF: 0.449 AC: 1560 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.75
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11788425; hg19: chr9-34333855;