ENST00000530902.5:n.165_167dupAGC

Variant names:

• chr5-146878727-A-AGCT
• rs10591869
• ENST00000530902.5:n.165_167dupAGC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000530902.5(PPP2R2B):​n.165_167dupAGC variant causes a non coding transcript exon 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 ENST00000530902.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 12

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-264_-262dupAGC		5_prime_UTR_variant	Exon 1 of 10	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.-264_-262dupAGC		5_prime_UTR_variant	Exon 1 of 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

African (AFR) AF: 0.00456 AC: 107 AN: 23462

American (AMR) AF: 0.00461 AC: 125 AN: 27120

Ashkenazi Jewish (ASJ) AF: 0.00282 AC: 43 AN: 15234

East Asian (EAS) AF: 0.00193 AC: 46 AN: 23778

South Asian (SAS) AF: 0.00913 AC: 661 AN: 72404

European-Finnish (FIN) AF: 0.00450 AC: 70 AN: 15550

Middle Eastern (MID) AF: 0.0127 AC: 36 AN: 2844

European-Non Finnish (NFE) AF: 0.0113 AC: 10431 AN: 922930

Other (OTH) AF: 0.00928 AC: 398 AN: 42876

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

African (AFR) AF: 0.00451 AC: 185 AN: 41004

American (AMR) AF: 0.00771 AC: 117 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00462 AC: 16 AN: 3460

East Asian (EAS) AF: 0.00509 AC: 25 AN: 4910

South Asian (SAS) AF: 0.00936 AC: 44 AN: 4700

European-Finnish (FIN) AF: 0.00479 AC: 50 AN: 10442

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0114 AC: 770 AN: 67632

Other (OTH) AF: 0.00958 AC: 20 AN: 2088

Alfa AF: 0.00 Hom.: 47

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPP2R2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10591869; hg19: chr5-146258290;