9-76703486-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015225.3(PRUNE2):c.8127G>C(p.Pro2709Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,613,216 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0052 ( 36 hom. )

Consequence

PRUNE2
NM_015225.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.64

Publications

1 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.005).

BP6

Variant 9-76703486-C-G is Benign according to our data. Variant chr9-76703486-C-G is described in ClinVar as [Benign]. Clinvar id is 772912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.64 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRUNE2	NM_015225.3 link	c.8127G>C	p.Pro2709Pro	synonymous_variant	Exon 9 of 19	ENST00000376718.8	NP_056040.2	Q8WUY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRUNE2	ENST00000376718.8 link	c.8127G>C	p.Pro2709Pro	synonymous_variant	Exon 9 of 19	5	NM_015225.3	ENSP00000365908.3		Q8WUY3-1

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

658

AN:

151662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000703

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00500

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00479

Gnomad FIN

AF:

0.00153

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00627

Gnomad OTH

AF:

0.00627

GnomAD2 exomes

AF:

0.00488

AC:

1209

AN:

247674

AF XY:

0.00510

show subpopulations

Gnomad AFR exome

AF:

0.000846

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00177

Gnomad NFE exome

AF:

0.00627

Gnomad OTH exome

AF:

0.00631

GnomAD4 exome

AF:

0.00519

AC:

7586

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

3776

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33478

American (AMR)

AF:

0.00373

AC:

167

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

495

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00472

AC:

407

AN:

86242

European-Finnish (FIN)

AF:

0.00191

AC:

102

AN:

53382

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00538

AC:

5982

AN:

1111674

Other (OTH)

AF:

0.00585

AC:

353

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

353

707

1060

1414

1767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00433

AC:

657

AN:

151780

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

307

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.000701

AC:

AN:

41394

American (AMR)

AF:

0.00499

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3468

East Asian (EAS)

AF:

0.000389

AC:

AN:

5142

South Asian (SAS)

AF:

0.00479

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00153

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00625

AC:

425

AN:

67978

Other (OTH)

AF:

0.00620

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00436

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.033

(source)

DANN

Benign

0.67

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

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

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9-76703486-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over