5-134201788-T-G

Variant names:

• chr5-134201788-T-G
• rs2302599
• NM_002715.4:c.486+60A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002715.4(PPP2CA):​c.486+60A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,541,796 control chromosomes in the GnomAD database, including 492,509 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 0.77 (45956 hom., cov: 34)
  • Exomes 𝑓: 0.80 (446553 hom.)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2CA	NM_002715.4	MANE Select	c.486+60A>C		intron	N/A	NP_002706.1
	PPP2CA	NM_001355019.2		c.291+60A>C		intron	N/A	NP_001341948.1
	PPP2CA	NR_149151.2		n.730+60A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2CA	ENST00000481195.6	TSL:1 MANE Select	c.486+60A>C		intron	N/A	ENSP00000418447.1
	ENSG00000272772	ENST00000519718.2	TSL:5	c.102+23972A>C		intron	N/A	ENSP00000430774.2
	ENSG00000273345	ENST00000703317.1		n.*457+60A>C		intron	N/A	ENSP00000515260.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117589 AN: 152054 Hom.: 45931 Cov.: 34

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.798 AC: 1109459 AN: 1389624 Hom.: 446553 AF XY: 0.797 AC XY: 551657 AN XY: 692474

African (AFR) AF: 0.774 AC: 23524 AN: 30390

American (AMR) AF: 0.527 AC: 18870 AN: 35780

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 19684 AN: 25256

East Asian (EAS) AF: 0.553 AC: 20772 AN: 37536

South Asian (SAS) AF: 0.727 AC: 57355 AN: 78926

European-Finnish (FIN) AF: 0.742 AC: 38856 AN: 52388

Middle Eastern (MID) AF: 0.767 AC: 4302 AN: 5610

European-Non Finnish (NFE) AF: 0.826 AC: 880875 AN: 1066118

Other (OTH) AF: 0.785 AC: 45221 AN: 57620

GnomAD4 genome AF: 0.773 AC: 117663 AN: 152172 Hom.: 45956 Cov.: 34 AF XY: 0.763 AC XY: 56759 AN XY: 74378

African (AFR) AF: 0.778 AC: 32270 AN: 41502

American (AMR) AF: 0.648 AC: 9901 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2861 AN: 5180

South Asian (SAS) AF: 0.742 AC: 3579 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7769 AN: 10588

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55944 AN: 68002

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.746 Hom.: 4904

Bravo AF: 0.763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		0.035
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: rs2302599; hg19: chr5-133537479; COSMIC: COSV51537884; COSMIC: COSV51537884;