chr9-76655459-C-T

Position:

chr9-76655459-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015225.3(PRUNE2):c.8320G>A(p.Gly2774Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,612,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PRUNE2
NM_015225.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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:

LOC105376095 (HGNC:):

LOC105376095 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0720799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRUNE2	NM_015225.3 linkuse as main transcript	c.8320G>A	p.Gly2774Ser	missense_variant	10/19	ENST00000376718.8
LOC105376095	XR_007061586.1 linkuse as main transcript	n.3362C>T		non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRUNE2	ENST00000376718.8 linkuse as main transcript	c.8320G>A	p.Gly2774Ser	missense_variant	10/19	5	NM_015225.3	P1	Q8WUY3-1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000486

AC:

AN:

246896

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134082

show subpopulations

Gnomad AFR exome

AF:

0.000722

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1460614

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726426

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000282

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000957

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000498

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.8320G>A (p.G2774S) alteration is located in exon 10 (coding exon 10) of the PRUNE2 gene. This alteration results from a G to A substitution at nucleotide position 8320, causing the glycine (G) at amino acid position 2774 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

.;.;T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.072

T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.3

.;.;M;.;.

MutationTaster

Benign

0.78

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

D;.;N;.;N

REVEL

Benign

0.23

Sift

Benign

0.27

T;.;D;.;D

Sift4G

Benign

0.62

T;T;D;D;D

Polyphen

0.98

.;.;D;.;.

Vest4

0.49

MVP

0.63

MPC

0.20

ClinPred

0.16

GERP RS

5.7

Varity_R

0.17

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over