5-146878727-AGCTGCTGCT-A

Position:

• chr5-146878727-AGCTGCTGCT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_181675.4(PPP2R2B):​c.-270_-262delAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,297,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (0 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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 5-146878727-AGCTGCTGCT-A is Benign according to our data. Variant chr5-146878727-AGCTGCTGCT-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-270_-262delAGCAGCAGC		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.-270_-262delAGCAGCAGC		5_prime_UTR_variant	1/10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.000512 AC: 77 AN: 150488 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000858

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000406

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.0000958

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000192 AC: 220 AN: 1146986 Hom.: 0 AF XY: 0.000180 AC XY: 101 AN XY: 562104

Gnomad4 AFR exome AF: 0.000682

Gnomad4 AMR exome AF: 0.0000368

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000294

Gnomad4 SAS exome AF: 0.0000827

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000198

Gnomad4 OTH exome AF: 0.000163

GnomAD4 genome AF: 0.000511 AC: 77 AN: 150606 Hom.: 0 Cov.: 0 AF XY: 0.000504 AC XY: 37 AN XY: 73474

Gnomad4 AFR AF: 0.00110

Gnomad4 AMR AF: 0.000857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000407

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.0000958

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.00

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;