5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_181675.4(PPP2R2B):​c.-264_-262dupAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,296,802 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (5 hom., cov: 0)
  • Exomes 𝑓: 0.010 (70 hom.)
• Consequence: PPP2R2B NM_181675.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 5-146878727-A-AGCT is Benign according to our data. Variant chr5-146878727-A-AGCT is described in ClinVar as [Benign]. Clinvar id is 2655887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1236 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-264_-262dupAGC		5_prime_UTR_variant	1/10	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.-264_-262dupAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1238 AN: 150486 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00450

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.00528

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.00479

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00968

GnomAD4 exome AF: 0.0104 AC: 11917 AN: 1146198 Hom.: 70 Cov.: 27 AF XY: 0.0103 AC XY: 5808 AN XY: 561668

Gnomad4 AFR exome AF: 0.00456

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00282

Gnomad4 EAS exome AF: 0.00193

Gnomad4 SAS exome AF: 0.00913

Gnomad4 FIN exome AF: 0.00450

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.00928

GnomAD4 genome AF: 0.00821 AC: 1236 AN: 150604 Hom.: 5 Cov.: 0 AF XY: 0.00800 AC XY: 588 AN XY: 73472

Gnomad4 AFR AF: 0.00451

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.00509

Gnomad4 SAS AF: 0.00936

Gnomad4 FIN AF: 0.00479

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00958

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PPP2R2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10591869; hg19: chr5-146258290;