rs3808574

Positions:

• chr8-26339107-T-C

Variant summary

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

The NM_002717.4(PPP2R2A):​c.180+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 730,466 control chromosomes in the GnomAD database, including 2,149 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 0.063 (468 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1681 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.180+120T>C		intron_variant		ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.180+120T>C		intron_variant		1	NM_002717.4	ENSP00000370113	P1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9604 AN: 152138 Hom.: 467 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.0532 AC: 30752 AN: 578210 Hom.: 1681 AF XY: 0.0541 AC XY: 16560 AN XY: 306376

Gnomad4 AFR exome AF: 0.0887

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0454

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.0894

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.0306

Gnomad4 OTH exome AF: 0.0591

GnomAD4 genome AF: 0.0631 AC: 9614 AN: 152256 Hom.: 468 Cov.: 32 AF XY: 0.0635 AC XY: 4729 AN XY: 74438

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0329

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0447 Hom.: 23

Bravo AF: 0.0714

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3808574; hg19: chr8-26196623;