8-26369870-C-G

Position:

• chr8-26369870-C-G

Variant summary

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

The NM_002717.4(PPP2R2A):​c.1065-264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,234 control chromosomes in the GnomAD database, including 189 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 0.045 (189 hom., cov: 32)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.1065-264C>G		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.1065-264C>G		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6822 AN: 152116 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0449 AC: 6834 AN: 152234 Hom.: 189 Cov.: 32 AF XY: 0.0471 AC XY: 3503 AN XY: 74410

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0234 Hom.: 7

Bravo AF: 0.0380

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.42

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: rs17400920; hg19: chr8-26227386;