rs11958187

Variant names:

• chr5-147055600-G-A
• rs11958187
• ENST00000394414.5:c.74+65C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-147055600-G-A
• chr5-147055600-G-T

Variant summary

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

The ENST00000394414.5(PPP2R2B):​c.74+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,406,188 control chromosomes in the GnomAD database, including 252,030 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 0.54 (23277 hom., cov: 30)
  • Exomes 𝑓: 0.60 (228753 hom.)
• Consequence: PPP2R2B ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 10 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)

ENSG00000286468 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181674.3	c.74+65C>T		intron_variant	Intron 1 of 9		NP_858060.2
PPP2R2B	NM_001271900.2	c.50+25459C>T		intron_variant	Intron 2 of 10		NP_001258829.1
PPP2R2B	NM_001271899.1	c.88+25459C>T		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.74+65C>T		intron_variant	Intron 1 of 9	1		ENSP00000377936.1
PPP2R2B	ENST00000394413.7	c.50+25459C>T		intron_variant	Intron 2 of 10	2		ENSP00000377935.4
PPP2R2B	ENST00000504198.5	c.88+25459C>T		intron_variant	Intron 2 of 9	2		ENSP00000421396.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82393 AN: 151624 Hom.: 23265 Cov.: 30

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.600 AC: 752484 AN: 1254446 Hom.: 228753 AF XY: 0.601 AC XY: 380916 AN XY: 633718

African (AFR) AF: 0.393 AC: 11362 AN: 28892

American (AMR) AF: 0.592 AC: 25821 AN: 43644

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 14877 AN: 24636

East Asian (EAS) AF: 0.287 AC: 11072 AN: 38516

South Asian (SAS) AF: 0.587 AC: 47648 AN: 81192

European-Finnish (FIN) AF: 0.593 AC: 31453 AN: 53014

Middle Eastern (MID) AF: 0.668 AC: 2956 AN: 4428

European-Non Finnish (NFE) AF: 0.622 AC: 576040 AN: 926670

Other (OTH) AF: 0.585 AC: 31255 AN: 53454

GnomAD4 genome AF: 0.543 AC: 82447 AN: 151742 Hom.: 23277 Cov.: 30 AF XY: 0.541 AC XY: 40099 AN XY: 74146

African (AFR) AF: 0.406 AC: 16814 AN: 41372

American (AMR) AF: 0.569 AC: 8669 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1543 AN: 5132

South Asian (SAS) AF: 0.575 AC: 2758 AN: 4794

European-Finnish (FIN) AF: 0.598 AC: 6282 AN: 10500

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.623 AC: 42314 AN: 67922

Other (OTH) AF: 0.582 AC: 1226 AN: 2106

Alfa AF: 0.601 Hom.: 36774

Bravo AF: 0.535

Asia WGS AF: 0.458 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		1.1
PromoterAI		-0.020	Neutral
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: rs11958187; hg19: chr5-146435163; COSMIC: COSV60758080;