9-76704827-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015225.3(PRUNE2):c.7447G>A(p.Val2483Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,591,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2483F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

PRUNE2
NM_015225.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.431

Publications

0 publications found

Variant links:

Genes affected

PRUNE2 (HGNC:25209): (prune homolog 2 with BCH domain) The protein encoded by this gene belongs to the B-cell CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose members play roles in many cellular processes including apotosis, cell transformation, and synaptic function. Several functions for this protein have been demonstrated including suppression of Ras homolog family member A activity, which results in reduced stress fiber formation and suppression of oncogenic cellular transformation. A high molecular weight isoform of this protein has also been shown to colocalize with Adaptor protein complex 2, beta-Adaptin and endodermal markers, suggesting an involvement in post-endocytic trafficking. In prostate cancer cells, this gene acts as a tumor suppressor and its expression is regulated by prostate cancer antigen 3, a non-protein coding gene on the opposite DNA strand in an intron of this gene. Prostate cancer antigen 3 regulates levels of this gene through formation of a double-stranded RNA that undergoes adenosine deaminase actin on RNA-dependent adenosine-to-inosine RNA editing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

PRUNE2 links:

PCA3 (HGNC:8637): (prostate cancer associated 3) This gene produces a spliced, long non-coding RNA that is highly overexpressed in most types of prostate cancer cells and is used as a specific biomarker for this type of cancer. This gene is embedded in an intronic region of the prune2 gene on the opposite DNA strand. The transcript regulates prune2 levels through formation of a double-stranded RNA that undergoes adenosine deaminase acting on RNA-dependent adenosine-to-inosine RNA editing. In prostate cancer derived cells, overexpression of PCA induced downregulation of prune2, leading to decreased cell proliferation. Conversely, silencing in prostate cancer cells resulted in increased proliferation. Regulation of this gene appears to be sensitive to androgen-receptor activation, a molecular signature of prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2017]

PCA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013723433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRUNE2	NM_015225.3	MANE Select	c.7447G>A	p.Val2483Ile	missense	Exon 8 of 19	NP_056040.2	Q8WUY3-1
PRUNE2	NM_001308048.2		c.7447G>A	p.Val2483Ile	missense	Exon 8 of 18	NP_001294977.1
PRUNE2	NM_001308047.2		c.7447G>A	p.Val2483Ile	missense	Exon 8 of 18	NP_001294976.1	A0A088AWP5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRUNE2	ENST00000376718.8	TSL:5 MANE Select	c.7447G>A	p.Val2483Ile	missense	Exon 8 of 19	ENSP00000365908.3	Q8WUY3-1
PRUNE2	ENST00000443509.6	TSL:5	c.7447G>A	p.Val2483Ile	missense	Exon 8 of 18	ENSP00000393843.3	A0A088AWP5
PRUNE2	ENST00000428286.5	TSL:5	c.6370G>A	p.Val2124Ile	missense	Exon 8 of 19	ENSP00000397425.1	E9PDC2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000929

AC:

AN:

215252

AF XY:

0.00000861

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1439274

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

713794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

41564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25630

East Asian (EAS)

AF:

0.00

AC:

AN:

39028

South Asian (SAS)

AF:

0.00

AC:

AN:

83058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000546

AC:

AN:

1099444

Other (OTH)

AF:

0.0000168

AC:

AN:

59576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.1

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0035

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.31

M_CAP

Benign

0.0031

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

PhyloP100

-0.43

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.020

REVEL

Benign

0.054

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.034

MutPred

0.079

Loss of disorder (P = 0.1887)

MVP

0.25

MPC

0.069

ClinPred

0.043

GERP RS

-0.63

Varity_R

0.026

gMVP

0.031

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over