chr8-26295607-A-G

Variant names:

• chr8-26295607-A-G
• rs12676426
• NM_002717.4:c.82+1867A>G

Variant summary

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

The NM_002717.4(PPP2R2A):​c.82+1867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,150 control chromosomes in the GnomAD database, including 5,029 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 0.23 (5029 hom., cov: 32)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 2 publications found

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) 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 an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002717.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	NM_002717.4	MANE Select	c.82+1867A>G		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.112+1867A>G		intron	N/A	NP_001171062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	ENST00000380737.8	TSL:1 MANE Select	c.82+1867A>G		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.112+1867A>G		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000665949.1		c.-432+1867A>G		intron	N/A	ENSP00000499648.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34381 AN: 152032 Hom.: 5026 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.226 AC: 34382 AN: 152150 Hom.: 5029 Cov.: 32 AF XY: 0.230 AC XY: 17083 AN XY: 74380

African (AFR) AF: 0.0552 AC: 2295 AN: 41544

American (AMR) AF: 0.215 AC: 3282 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3466

East Asian (EAS) AF: 0.148 AC: 765 AN: 5180

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4824

European-Finnish (FIN) AF: 0.373 AC: 3934 AN: 10556

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21473 AN: 67974

Other (OTH) AF: 0.222 AC: 467 AN: 2108

Alfa AF: 0.274 Hom.: 854

Bravo AF: 0.203

Asia WGS AF: 0.197 AC: 681 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.43
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: rs12676426; hg19: chr8-26153123;