5-146941260-G-T

Variant names:

• chr5-146941260-G-T
• rs1864982
• ENST00000394414.5:c.75-63065C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000394414.5(PPP2R2B):​c.75-63065C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,958 control chromosomes in the GnomAD database, including 4,393 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 0.22 (4393 hom., cov: 32)
• Consequence: PPP2R2B ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 17 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181674.3	c.75-63065C>A		intron_variant	Intron 1 of 9		NP_858060.2
PPP2R2B	NM_001271900.2	c.51-63065C>A		intron_variant	Intron 2 of 10		NP_001258829.1
PPP2R2B	NM_001271899.1	c.88+139799C>A		intron_variant	Intron 2 of 9		NP_001258828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394414.5	c.75-63065C>A		intron_variant	Intron 1 of 9	1		ENSP00000377936.1
PPP2R2B	ENST00000394413.7	c.51-63065C>A		intron_variant	Intron 2 of 10	2		ENSP00000377935.4
PPP2R2B	ENST00000504198.5	c.88+139799C>A		intron_variant	Intron 2 of 9	2		ENSP00000421396.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32838 AN: 151840 Hom.: 4383 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.216 AC: 32864 AN: 151958 Hom.: 4393 Cov.: 32 AF XY: 0.217 AC XY: 16091 AN XY: 74252

African (AFR) AF: 0.378 AC: 15638 AN: 41386

American (AMR) AF: 0.194 AC: 2961 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1397 AN: 5152

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4810

European-Finnish (FIN) AF: 0.105 AC: 1110 AN: 10570

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9197 AN: 67990

Other (OTH) AF: 0.217 AC: 459 AN: 2116

Alfa AF: 0.169 Hom.: 9113

Bravo AF: 0.232

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.62
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1864982; hg19: chr5-146320823;