rs254048

Variant names:

• chr5-134214224-C-T
• rs254048
• NM_002715.4:c.103-8093G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

PPP2CA Gene-Disease associations (from GenCC):

• Houge-Janssens syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000272772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.103-8093G>A		intron_variant	Intron 1 of 6	ENST00000481195.6	NP_002706.1
PPP2CA	NM_001355019.2	c.-93-8093G>A		intron_variant	Intron 1 of 6		NP_001341948.1
PPP2CA	NR_149151.2	n.347-8093G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.103-8093G>A		intron_variant	Intron 1 of 6	1	NM_002715.4	ENSP00000418447.1
ENSG00000272772	ENST00000519718.2	c.102+11536G>A		intron_variant	Intron 1 of 5	5		ENSP00000430774.2
ENSG00000273345	ENST00000703317.1	n.*74-8093G>A		intron_variant	Intron 4 of 9			ENSP00000515260.1

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

African (AFR) AF: 0.711 AC: 29473 AN: 41478

American (AMR) AF: 0.629 AC: 9605 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2858 AN: 5170

South Asian (SAS) AF: 0.733 AC: 3541 AN: 4830

European-Finnish (FIN) AF: 0.731 AC: 7726 AN: 10572

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55473 AN: 68010

Other (OTH) AF: 0.731 AC: 1542 AN: 2110

Alfa AF: 0.781 Hom.: 6029

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
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs254048; hg19: chr5-133549915;