rs2164027

Variant names:

• chr8-26355064-A-G
• rs2164027
• NM_002717.4:c.346+431A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002717.4(PPP2R2A):​c.346+431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,162 control chromosomes in the GnomAD database, including 5,036 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 (5036 hom., cov: 32)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.346+431A>G		intron_variant	Intron 4 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.346+431A>G		intron_variant	Intron 4 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34886 AN: 152046 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.229 AC: 34892 AN: 152162 Hom.: 5036 Cov.: 32 AF XY: 0.233 AC XY: 17312 AN XY: 74376

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.226

Alfa AF: 0.275 Hom.: 847

Bravo AF: 0.208

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2164027; hg19: chr8-26212580;