ENST00000530902.5:n.150_167delAGCAGCAGCAGCAGCAGC

Variant names:

• chr5-146878727-AGCTGCTGCTGCTGCTGCT-A
• rs10591869
• ENST00000530902.5:n.150_167delAGCAGCAGCAGCAGCAGC

Variant summary

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

The ENST00000530902.5(PPP2R2B):​n.150_167delAGCAGCAGCAGCAGCAGC 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 0.000166 in 1,297,602 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PPP2R2B ENST00000530902.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter U:1 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-AGCTGCTGCTGCTGCTGCT-A is Benign according to our data. Variant chr5-146878727-AGCTGCTGCTGCTGCTGCT-A is described in ClinVar as [Benign]. Clinvar id is 1050601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-279_-262delAGCAGCAGCAGCAGCAGC		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.-279_-262delAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 23 AN: 150488 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000813

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 192 AN: 1146996 Hom.: 0 AF XY: 0.000169 AC XY: 95 AN XY: 562102

African (AFR) AF: 0.00 AC: 0 AN: 23470

American (AMR) AF: 0.00 AC: 0 AN: 27150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15242

East Asian (EAS) AF: 0.000126 AC: 3 AN: 23798

South Asian (SAS) AF: 0.000317 AC: 23 AN: 72534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15564

Middle Eastern (MID) AF: 0.000351 AC: 1 AN: 2848

European-Non Finnish (NFE) AF: 0.000173 AC: 160 AN: 923476

Other (OTH) AF: 0.000117 AC: 5 AN: 42914

GnomAD4 genome AF: 0.000153 AC: 23 AN: 150606 Hom.: 0 Cov.: 0 AF XY: 0.000163 AC XY: 12 AN XY: 73474

African (AFR) AF: 0.0000732 AC: 3 AN: 41004

American (AMR) AF: 0.00 AC: 0 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000815 AC: 4 AN: 4910

South Asian (SAS) AF: 0.00106 AC: 5 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000163 AC: 11 AN: 67634

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 47

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1 Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPP2R2B: BS1, BS2 -

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The PPP2R2B p.Ser14_Ser19del variant was not identified in the literature nor was it identified in dbSNP, ClinVar, Cosmic, LOVD 3.0 or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). This variant is an in-frame deletion resulting in the removal of six serine (ser) residues from codon 14 to 19; the impact of this alteration on PPP2R2B protein function is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=290/10	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;