rs193920858

Variant names:

• chr22-50440025-C-T
• rs193920858
• NM_001242898.2:c.2350C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 14/22 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.13
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.113844216).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6R2	NM_001242898.2	MANE Select	c.2350C>T	p.Arg784Trp	missense	Exon 21 of 24	NP_001229827.1	O75170-5
	PPP6R2	NM_001365836.1		c.2350C>T	p.Arg784Trp	missense	Exon 23 of 26	NP_001352765.1	O75170-1
	PPP6R2	NM_001351641.2		c.2353C>T	p.Arg785Trp	missense	Exon 21 of 24	NP_001338570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP6R2	ENST00000612753.5	TSL:2 MANE Select	c.2350C>T	p.Arg784Trp	missense	Exon 21 of 24	ENSP00000478417.1	O75170-5
	PPP6R2	ENST00000216061.9	TSL:1	c.2350C>T	p.Arg784Trp	missense	Exon 22 of 25	ENSP00000216061.5	O75170-1
	PPP6R2	ENST00000395741.7	TSL:1	c.2272C>T	p.Arg758Trp	missense	Exon 20 of 23	ENSP00000379090.3	O75170-3

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152246 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.0000559 AC: 14 AN: 250386 AF XY: 0.0000590

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 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.: 0 Cov.: 32 AF XY: 0.000147 AC XY: 107 AN XY: 726796

African (AFR) AF: 0.000149 AC: 5 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52766

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.000187 AC: 208 AN: 1111832

Other (OTH) AF: 0.000282 AC: 17 AN: 60362

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152246 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74376

African (AFR) AF: 0.000121 AC: 5 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.086
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.017	D
Polyphen		0.98	D
Vest4		0.17
MVP		0.082
MPC		0.044
ClinPred		0.11	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.24
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs193920858; hg19: chr22-50878454; COSMIC: COSV99323955; COSMIC: COSV99323955;