ENST00000530902.5:n.165_167delAGC

Variant names:

• chr5-146878727-AGCT-A
• rs10591869
• ENST00000530902.5:n.165_167delAGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000530902.5(PPP2R2B):​n.165_167delAGC 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 0.0304 in 1,278,638 control chromosomes in the GnomAD database, including 1,618 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (1019 hom., cov: 0)
  • Exomes 𝑓: 0.024 (599 hom.)
• Consequence: PPP2R2B ENST00000530902.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-146878727-AGCT-A is Benign according to our data. Variant chr5-146878727-AGCT-A is described in ClinVar as [Benign]. Clinvar id is 3056407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-264_-262delAGC		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_-262delAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11406 AN: 150414 Hom.: 1015 Cov.: 0

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0100

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0454

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0770

GnomAD4 exome AF: 0.0243 AC: 27398 AN: 1128108 Hom.: 599 AF XY: 0.0231 AC XY: 12775 AN XY: 552356

African (AFR) AF: 0.163 AC: 3744 AN: 23014

American (AMR) AF: 0.00923 AC: 247 AN: 26760

Ashkenazi Jewish (ASJ) AF: 0.0232 AC: 347 AN: 14960

East Asian (EAS) AF: 0.00447 AC: 106 AN: 23688

South Asian (SAS) AF: 0.00952 AC: 681 AN: 71530

European-Finnish (FIN) AF: 0.00856 AC: 131 AN: 15298

Middle Eastern (MID) AF: 0.0266 AC: 75 AN: 2824

European-Non Finnish (NFE) AF: 0.0230 AC: 20879 AN: 907746

Other (OTH) AF: 0.0281 AC: 1188 AN: 42288

GnomAD4 genome AF: 0.0759 AC: 11427 AN: 150530 Hom.: 1019 Cov.: 0 AF XY: 0.0736 AC XY: 5403 AN XY: 73430

African (AFR) AF: 0.213 AC: 8709 AN: 40966

American (AMR) AF: 0.0361 AC: 548 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.0454 AC: 157 AN: 3458

East Asian (EAS) AF: 0.0226 AC: 111 AN: 4910

South Asian (SAS) AF: 0.0128 AC: 60 AN: 4698

European-Finnish (FIN) AF: 0.00575 AC: 60 AN: 10428

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.0237 AC: 1604 AN: 67622

Other (OTH) AF: 0.0761 AC: 159 AN: 2088

Alfa AF: 0.0120 Hom.: 47

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PPP2R2B-related disorder Benign:1

May 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV109430722; COSMIC: COSV109430722;