5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_181675.4(PPP2R2B):​c.-262_-261insAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,289,898 control chromosomes in the GnomAD database, including 7,109 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1619 hom., cov: 0)
  • Exomes 𝑓: 0.13 (5490 hom.)
• Consequence: PPP2R2B NM_181675.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-262_-261insAGCAGCAGC		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.-262_-261insAGCAGCAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933	P3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21147 AN: 150410 Hom.: 1617 Cov.: 0

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.125 AC: 142786 AN: 1139370 Hom.: 5490 Cov.: 27 AF XY: 0.128 AC XY: 71407 AN XY: 558292

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.0878

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.141 AC: 21167 AN: 150528 Hom.: 1619 Cov.: 0 AF XY: 0.141 AC XY: 10351 AN XY: 73434

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.162

ClinVar

Not reported in ClinVar

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;