chr5-134194449-A-G

Position:

• chr5-134194449-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.*3323T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 152,288 control chromosomes in the GnomAD database, including 795 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 0.095 (795 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: PPP2CA NM_002715.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.*3323T>C		3_prime_UTR_variant	7/7	ENST00000481195.6	NP_002706.1
PPP2CA	NM_001355019.2	c.*3323T>C		3_prime_UTR_variant	7/7		NP_001341948.1
PPP2CA	NR_149151.2	n.4508T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.*3323T>C		3_prime_UTR_variant	7/7	1	NM_002715.4	ENSP00000418447	P4
PPP2CA	ENST00000703354.1	c.*3323T>C		3_prime_UTR_variant	7/7			ENSP00000515268	A1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14494 AN: 152156 Hom.: 790 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0953 AC: 14513 AN: 152274 Hom.: 795 Cov.: 32 AF XY: 0.101 AC XY: 7501 AN XY: 74452

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0858 Hom.: 225

Bravo AF: 0.0984

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.8
DANN	Benign	0.89

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: rs10491322; hg19: chr5-133530140;