rs3895755

Positions:

• chr5-134225648-A-G

Variant summary

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

The NM_002715.4(PPP2CA):​c.102+112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 886,418 control chromosomes in the GnomAD database, including 3,189 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 0.099 (880 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2309 hom.)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

Genes affected

PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) This gene encodes the phosphatase 2A catalytic subunit. 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. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

ENSG00000272772 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.102+112T>C		intron_variant		ENST00000481195.6	NP_002706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.102+112T>C		intron_variant		1	NM_002715.4	ENSP00000418447.1
ENSG00000272772	ENST00000519718.2	c.102+112T>C		intron_variant		5		ENSP00000430774.2
ENSG00000273345	ENST00000703317.1	n.*73+17244T>C		intron_variant				ENSP00000515260.1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 14989 AN: 151244 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0701 AC: 51522 AN: 735054 Hom.: 2309 Cov.: 10 AF XY: 0.0712 AC XY: 26512 AN XY: 372502

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.0721

Gnomad4 EAS exome AF: 0.0498

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0992 AC: 15012 AN: 151364 Hom.: 880 Cov.: 32 AF XY: 0.105 AC XY: 7760 AN XY: 73994

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0383 Hom.: 30

Bravo AF: 0.102

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3895755; hg19: chr5-133561339;