Variant 5-146697963-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_181675.4(PPP2R2B):c.334+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,597,466 control chromosomes in the GnomAD database, including 21,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2511 hom., cov: 31)

Exomes 𝑓: 0.16 ( 19046 hom. )

Consequence

PPP2R2B
NM_181675.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

PPP2R2B (HGNC:9305): (protein phosphatase 2 regulatory subunit Bbeta) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a beta isoform of the regulatory subunit B55 subfamily. Defects in this gene cause autosomal dominant spinocerebellar ataxia 12 (SCA12), a disease caused by degeneration of the cerebellum, sometimes involving the brainstem and spinal cord, and in resulting in poor coordination of speech and body movements. Multiple alternatively spliced variants, which encode different isoforms, have been identified for this gene. The 5' UTR of some of these variants includes a CAG trinucleotide repeat sequence (7-28 copies) that can be expanded to 55-78 copies in cases of SCA12. [provided by RefSeq, Jul 2016]

PPP2R2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-146697963-C-T is Benign according to our data. Variant chr5-146697963-C-T is described in ClinVar as [Benign]. Clinvar id is 1272737.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4 linkuse as main transcript	c.334+16G>A		intron_variant		ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9 linkuse as main transcript	c.334+16G>A		intron_variant		2	NM_181675.4	ENSP00000377933	P3	Q00005-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26754

AN:

151780

Hom.:

2510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.169

AC:

40081

AN:

236964

Hom.:

3658

AF XY:

0.165

AC XY:

21149

AN XY:

128190

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.158

AC:

228982

AN:

1445568

Hom.:

19046

Cov.:

AF XY:

0.158

AC XY:

113283

AN XY:

718994

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.176

AC:

26767

AN:

151898

Hom.:

2511

Cov.:

AF XY:

0.176

AC XY:

13029

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.0954

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.147

Hom.:

2964

Bravo

AF:

0.186

Asia WGS

AF:

0.216

AC:

750

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 27, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.069

DANN

Benign

0.31

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