5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCT

Position:

• chr5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_181675.4(PPP2R2B):​c.-267_-262delAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000966 in 1,297,202 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0051 (8 hom., cov: 0)
  • Exomes 𝑓: 0.00043 (2 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]

PPP2R2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (763/150598) while in subpopulation AFR AF= 0.0171 (701/40998). AF 95% confidence interval is 0.016. There are 8 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-267_-262delAGCAGC		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.-267_-262delAGCAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.00506 AC: 762 AN: 150480 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000237

Gnomad OTH AF: 0.00532

GnomAD4 exome AF: 0.000427 AC: 490 AN: 1146604 Hom.: 2 AF XY: 0.000399 AC XY: 224 AN XY: 561906

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000221

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000420

Gnomad4 SAS exome AF: 0.000110

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.000699

GnomAD4 genome AF: 0.00507 AC: 763 AN: 150598 Hom.: 8 Cov.: 0 AF XY: 0.00487 AC XY: 358 AN XY: 73470

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00211

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000237

Gnomad4 OTH AF: 0.00527

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;