rs254048

Positions:

• chr5-134214224-C-T

Variant summary

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

The NM_002715.4(PPP2CA):​c.103-8093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,122 control chromosomes in the GnomAD database, including 43,005 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 0.75 (43005 hom., cov: 33)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.103-8093G>A		intron_variant		ENST00000481195.6	NP_002706.1
PPP2CA	NM_001355019.2	c.-93-8093G>A		intron_variant			NP_001341948.1
PPP2CA	NR_149151.2	n.347-8093G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.103-8093G>A		intron_variant		1	NM_002715.4	ENSP00000418447	P4

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113731 AN: 152004 Hom.: 42981 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.748 AC: 113805 AN: 152122 Hom.: 43005 Cov.: 33 AF XY: 0.739 AC XY: 54927 AN XY: 74372

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.731

Alfa AF: 0.782 Hom.: 5804

Bravo AF: 0.734

Asia WGS AF: 0.663 AC: 2309 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	1.9
DANN	Benign	0.44

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: rs254048; hg19: chr5-133549915;