5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_181675.4(PPP2R2B):​c.-279_-262dupAGCAGCAGCAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.029 (193 hom., cov: 0)
  • Exomes 𝑓: 0.022 (2642 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R2B NM_181675.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided 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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 5-146878727-A-AGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr5-146878727-A-AGCTGCTGCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 3059028.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-279_-262dupAGCAGCAGCAGCAGCAGC		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.-279_-262dupAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4312 AN: 150468 Hom.: 192 Cov.: 0

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0198

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0281

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0222 AC: 25400 AN: 1143696 Hom.: 2642 Cov.: 27 AF XY: 0.0224 AC XY: 12562 AN XY: 560538

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.00834

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0298

GnomAD4 genome AF: 0.0287 AC: 4326 AN: 150586 Hom.: 193 Cov.: 0 AF XY: 0.0316 AC XY: 2323 AN XY: 73466

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0937

Gnomad4 ASJ AF: 0.00318

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0204

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0278

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PPP2R2B-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 04, 2022

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

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;