rs609412

Variant names:

• chr5-146845681-A-G
• rs609412
• NM_181675.4:c.70+32321T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181675.4(PPP2R2B):​c.70+32321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,096 control chromosomes in the GnomAD database, including 11,637 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11637 hom., cov: 32)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 12

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.70+32321T>C		intron_variant	Intron 2 of 9	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.70+32321T>C		intron_variant	Intron 2 of 9	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54152 AN: 151976 Hom.: 11623 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54217 AN: 152096 Hom.: 11637 Cov.: 32 AF XY: 0.358 AC XY: 26632 AN XY: 74376

African (AFR) AF: 0.580 AC: 24029 AN: 41454

American (AMR) AF: 0.344 AC: 5260 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3039 AN: 5186

South Asian (SAS) AF: 0.401 AC: 1929 AN: 4816

European-Finnish (FIN) AF: 0.219 AC: 2323 AN: 10592

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15406 AN: 67984

Other (OTH) AF: 0.337 AC: 712 AN: 2110

Alfa AF: 0.274 Hom.: 31730

Bravo AF: 0.376

Asia WGS AF: 0.472 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.048
DANN	Benign	0.38
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs609412; hg19: chr5-146225244; COSMIC: COSV60765015;