rs7142002

Positions:

• chr14-101894408-T-C

Variant summary

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

The NM_001352913.2(PPP2R5C):​c.964-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,139,104 control chromosomes in the GnomAD database, including 3,792 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 0.10 (1283 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2509 hom.)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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]

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 (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.964-99T>C		intron_variant		ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.964-99T>C		intron_variant			NM_001352913.2	ENSP00000511581	P3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15794 AN: 152130 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0951

GnomAD4 exome AF: 0.0605 AC: 59702 AN: 986856 Hom.: 2509 AF XY: 0.0583 AC XY: 29548 AN XY: 506694

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.0599

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0260

Gnomad4 FIN exome AF: 0.0279

Gnomad4 NFE exome AF: 0.0549

Gnomad4 OTH exome AF: 0.0726

GnomAD4 genome AF: 0.104 AC: 15819 AN: 152248 Hom.: 1283 Cov.: 32 AF XY: 0.100 AC XY: 7448 AN XY: 74440

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0675 Hom.: 849

Bravo AF: 0.115

Asia WGS AF: 0.100 AC: 349 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	1.7
DANN	Benign	0.58

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: rs7142002; hg19: chr14-102360745; COSMIC: COSV58269359; COSMIC: COSV58269359;