rs2738364

chrX-341404-G-CchrX-341404-G-T

Variant summary

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

The NM_013239.5(PPP2R3B):c.1086-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,611,780 control chromosomes in the GnomAD database, including 513,198 homozygotes. There are 638,742 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (48997 hom., 59354 hem., cov: 34)
  • Exomes 𝑓: 0.80 (464201 hom. 579388 hem.)
• Consequence: PPP2R3B NM_013239.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

PPP2R3B (HGNC:13417): (protein phosphatase 2 regulatory subunit B''beta) Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the beta subfamily of regulatory subunit B''. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R3B	NM_013239.5	c.1086-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000390665.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R3B	ENST00000390665.9	c.1086-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_013239.5	P1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121744 AN: 152048 Hom.: 48980 Cov.: 34 AF XY: 0.798 AC XY: 59273 AN XY: 74254

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.811

GnomAD3 exomes AF: 0.780 AC: 193521 AN: 248100 Hom.: 76239 AF XY: 0.789 AC XY: 106469 AN XY: 135022

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.822

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.803

GnomAD4 exome AF: 0.797 AC: 1162618 AN: 1459614 Hom.: 464201 Cov.: 44 AF XY: 0.798 AC XY: 579388 AN XY: 726022

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.820

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.798

GnomAD4 genome AF: 0.800 AC: 121805 AN: 152166 Hom.: 48997 Cov.: 34 AF XY: 0.798 AC XY: 59354 AN XY: 74382

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.806

Bravo AF: 0.796

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.39
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2738364; hg19: chrX-302139;