rs200415574

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001242898.2(PPP6R2):c.2599C>T(p.Arg867Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,583,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R867Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PPP6R2
NM_001242898.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222

Publications

1 publications found

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:

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

SBF1 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4B3
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia, Ambry Genetics

SBF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046221465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242898.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP6R2	NM_001242898.2	MANE Select	c.2599C>T	p.Arg867Trp	missense	Exon 23 of 24	NP_001229827.1	O75170-5
PPP6R2	NM_001365836.1		c.2620C>T	p.Arg874Trp	missense	Exon 25 of 26	NP_001352765.1	O75170-1
PPP6R2	NM_001351641.2		c.2602C>T	p.Arg868Trp	missense	Exon 23 of 24	NP_001338570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP6R2	ENST00000612753.5	TSL:2 MANE Select	c.2599C>T	p.Arg867Trp	missense	Exon 23 of 24	ENSP00000478417.1	O75170-5
PPP6R2	ENST00000216061.9	TSL:1	c.2620C>T	p.Arg874Trp	missense	Exon 24 of 25	ENSP00000216061.5	O75170-1
PPP6R2	ENST00000395741.7	TSL:1	c.2521C>T	p.Arg841Trp	missense	Exon 22 of 23	ENSP00000379090.3	O75170-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000396

AC:

AN:

201862

AF XY:

0.0000273

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000260

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1431440

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

709624

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32638

American (AMR)

AF:

0.00

AC:

AN:

41386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25612

East Asian (EAS)

AF:

0.000291

AC:

AN:

37854

South Asian (SAS)

AF:

0.0000603

AC:

AN:

82922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5070

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1096842

Other (OTH)

AF:

0.0000339

AC:

AN:

59012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000775

AC:

AN:

5162

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.22

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.072

Sift

Uncertain

0.013

Sift4G

Uncertain

0.016

Polyphen

0.95

Vest4

0.28

MVP

0.043

MPC

0.045

ClinPred

0.22

GERP RS

2.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.091

gMVP

0.26

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over