Variant 2-44201251-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002706.6(PPM1B):c.52G>A(p.Ala18Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,613,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

PPM1B
NM_002706.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.88

Variant links:

Genes affected

PPM1B (HGNC:9276): (protein phosphatase, Mg2+/Mn2+ dependent 1B) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [provided by RefSeq, Jul 2008]

PPM1B links:

PPM1B (HGNC:):

PPM1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008306444).

BP6

Variant 2-44201251-G-A is Benign according to our data. Variant chr2-44201251-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 785963.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1B	NM_002706.6 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	2/6	ENST00000282412.9	NP_002697.1	O75688-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1B	ENST00000282412.9 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	2/6	1	NM_002706.6	ENSP00000282412.4		O75688-1
ENSG00000285542	ENST00000649044.1 linkuse as main transcript	n.52G>A		non_coding_transcript_exon_variant	2/15			ENSP00000497083.1		A0A3B3IS24

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000443

AC:

111

AN:

250734

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.000638

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:

0.0000176

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000121

AC:

177

AN:

1460788

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726504

show subpopulations

Gnomad4 AFR exome

AF:

0.00359

Gnomad4 AMR exome

AF:

0.000717

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:

0.00000180

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00126

AC:

192

AN:

152266

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00421

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

.;.;T;.;T

Eigen

Benign

-0.050

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;D;D

MetaRNN

Benign

0.0083

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.18

.;N;N;N;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.13

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.43

T;T;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T

Polyphen

0.0010, 0.0030

.;.;B;B;.

Vest4

0.049, 0.061, 0.052

MVP

0.42

MPC

0.14

ClinPred

0.026

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.13

gMVP

0.29

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