5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Position:

• chr5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_181675.4(PPP2R2B):​c.-262_-261insAGCAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (862 hom., cov: 0)
  • Exomes 𝑓: 0.081 (2938 hom.)
  • Failed GnomAD Quality Control
• 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 (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14251 AN: 150420 Hom.: 864 Cov.: 0

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0344

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0790

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0814 AC: 92384 AN: 1134862 Hom.: 2938 Cov.: 27 AF XY: 0.0816 AC XY: 45346 AN XY: 555830

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0608

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0415

Gnomad4 SAS exome AF: 0.0940

Gnomad4 FIN exome AF: 0.0729

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0865

GnomAD4 genome AF: 0.0948 AC: 14273 AN: 150538 Hom.: 862 Cov.: 0 AF XY: 0.0933 AC XY: 6852 AN XY: 73444

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.0582

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.0781

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;