rs3779915

Positions:

• chr8-26354736-G-C

Variant summary

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

The NM_002717.4(PPP2R2A):​c.346+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,143,566 control chromosomes in the GnomAD database, including 1,158 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 0.027 (250 hom., cov: 32)
  • Exomes 𝑓: 0.017 (908 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.346+103G>C		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.346+103G>C		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152104 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0168 AC: 16644 AN: 991344 Hom.: 908 AF XY: 0.0168 AC XY: 8096 AN XY: 482898

Gnomad4 AFR exome AF: 0.00301

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.00773

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0741

Gnomad4 FIN exome AF: 0.00857

Gnomad4 NFE exome AF: 0.00690

Gnomad4 OTH exome AF: 0.0226

GnomAD4 genome AF: 0.0270 AC: 4115 AN: 152222 Hom.: 250 Cov.: 32 AF XY: 0.0300 AC XY: 2231 AN XY: 74428

Gnomad4 AFR AF: 0.00597

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.00950

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0221 Hom.: 22

Bravo AF: 0.0363

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.77

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: rs3779915; hg19: chr8-26212252; COSMIC: COSV60099311; COSMIC: COSV60099311;