Variant 5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_181675.4(PPP2R2B):c.-288_-262dupAGCAGCAGCAGCAGCAGCAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 7 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 101 hom. )

Failed GnomAD Quality Control

Consequence

PPP2R2B
NM_181675.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 5-146878727-A-AGCTGCTGCTGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr5-146878727-A-AGCTGCTGCTGCTGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 2655889.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 707 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4 link	c.-288_-262dupAGCAGCAGCAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	1/10	ENST00000394411.9	NP_858061.3	Q00005-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9 link	c.-288_-262dupAGCAGCAGCAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933.3		Q00005-1

Frequencies

GnomAD3 genomes

AF:

0.00471

AC:

709

AN:

150482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00222

Gnomad AMR

AF:

0.00205

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.00978

Gnomad FIN

AF:

0.00125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00290

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00172

AC:

1968

AN:

1146160

Hom.:

101

Cov.:

AF XY:

0.00191

AC XY:

1072

AN XY:

561678

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.000590

Gnomad4 EAS exome

AF:

0.00799

Gnomad4 SAS exome

AF:

0.00680

Gnomad4 FIN exome

AF:

0.0198

Gnomad4 NFE exome

AF:

0.000595

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.00469

AC:

707

AN:

150600

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

356

AN XY:

73472

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00387

Gnomad4 SAS

AF:

0.00937

Gnomad4 FIN

AF:

0.00125

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00287

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

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

PPP2R2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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