rs1895360

Variant names:

• chr5-146641480-T-C
• rs1895360
• NM_181675.4:c.626-3065A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-146641480-T-C
• chr5-146641480-T-G

Variant summary

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

The NM_181675.4(PPP2R2B):​c.626-3065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 151,100 control chromosomes in the GnomAD database, including 70,512 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 0.97 (70512 hom., cov: 27)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 2 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 = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.626-3065A>G		intron_variant	Intron 6 of 9	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.626-3065A>G		intron_variant	Intron 6 of 9	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.965 AC: 145777 AN: 150990 Hom.: 70474 Cov.: 27

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.973

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

GnomAD4 genome AF: 0.965 AC: 145870 AN: 151100 Hom.: 70512 Cov.: 27 AF XY: 0.967 AC XY: 71258 AN XY: 73718

African (AFR) AF: 0.905 AC: 36960 AN: 40822

American (AMR) AF: 0.984 AC: 14972 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3435 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5129 AN: 5130

South Asian (SAS) AF: 0.975 AC: 4672 AN: 4790

European-Finnish (FIN) AF: 0.998 AC: 10319 AN: 10344

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.987 AC: 67153 AN: 68014

Other (OTH) AF: 0.973 AC: 2046 AN: 2102

Alfa AF: 0.973 Hom.: 9449

Bravo AF: 0.961

Asia WGS AF: 0.983 AC: 3415 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-0.56
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: rs1895360; hg19: chr5-146021043;