rs2749907

Positions:

• chr14-101879356-G-A

Variant summary

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

The NM_001352913.2(PPP2R5C):​c.460-2805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,604 control chromosomes in the GnomAD database, including 12,115 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 0.35 (12100 hom., cov: 32)
  • Exomes 𝑓: 0.21 (15 hom.)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

Genes affected

PPP2R5C (HGNC:9311): (protein phosphatase 2 regulatory subunit B'gamma) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 a gamma isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.460-2805G>A		intron_variant		ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.460-2805G>A		intron_variant			NM_001352913.2	ENSP00000511581.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53252 AN: 152014 Hom.: 12069 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.215 AC: 101 AN: 470 Hom.: 15 Cov.: 0 AF XY: 0.216 AC XY: 77 AN XY: 356

Gnomad4 AFR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.351 AC: 53330 AN: 152134 Hom.: 12100 Cov.: 32 AF XY: 0.347 AC XY: 25773 AN XY: 74370

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.338

Alfa AF: 0.237 Hom.: 9338

Bravo AF: 0.364

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.62

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: rs2749907; hg19: chr14-102345693;