Variant rs193920858 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001242898.2(PPP6R2):c.2350C>T(p.Arg784Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PPP6R2
NM_001242898.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

PPP6R2 (HGNC:19253): (protein phosphatase 6 regulatory subunit 2) The protein encoded by this gene is a regulatory protein for the protein phosphatase-6 catalytic subunit. Together, these proteins act as a significant T-loop phosphatase for Aurora A, an essential mitotic kinase. Loss of function of either the regulatory or catalytic subunit of protein phosphatase-6 interferes with spindle formation and chromosome alignment. [provided by RefSeq, May 2017]

PPP6R2 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=0.113844216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP6R2	NM_001242898.2 linkuse as main transcript	c.2350C>T	p.Arg784Trp	missense_variant	21/24	ENST00000612753.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP6R2	ENST00000612753.5 linkuse as main transcript	c.2350C>T	p.Arg784Trp	missense_variant	21/24	2	NM_001242898.2	A2	O75170-5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000559

AC:

AN:

250386

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1460944

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000112

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Malignant tumor of prostate

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.81

T;T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.4

N;.;N;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.017

D;.;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

0.98

D;D;D;D;P

Vest4

0.17

MVP

0.082

MPC

0.044

ClinPred

0.11

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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