5-134204379-A-G

Variant names:

• chr5-134204379-A-G
• rs7705319
• NM_002715.4:c.312+1543T>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.312+1543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,222 control chromosomes in the GnomAD database, including 45,967 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 (45967 hom., cov: 34)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• 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=-0.9).
• 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.312+1543T>C		intron	N/A	NP_002706.1
	PPP2CA	NM_001355019.2		c.117+1543T>C		intron	N/A	NP_001341948.1
	PPP2CA	NR_149151.2		n.556+1543T>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.312+1543T>C		intron	N/A	ENSP00000418447.1
	ENSG00000272772	ENST00000519718.2	TSL:5	c.102+21381T>C		intron	N/A	ENSP00000430774.2
	ENSG00000273345	ENST00000703317.1		n.*283+1543T>C		intron	N/A	ENSP00000515260.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117622 AN: 152102 Hom.: 45942 Cov.: 34

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.773 AC: 117697 AN: 152222 Hom.: 45967 Cov.: 34 AF XY: 0.763 AC XY: 56793 AN XY: 74418

African (AFR) AF: 0.777 AC: 32275 AN: 41520

American (AMR) AF: 0.648 AC: 9907 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2863 AN: 5182

South Asian (SAS) AF: 0.742 AC: 3584 AN: 4828

European-Finnish (FIN) AF: 0.734 AC: 7772 AN: 10592

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

European-Non Finnish (NFE) AF: 0.823 AC: 55955 AN: 68014

Other (OTH) AF: 0.756 AC: 1600 AN: 2116

Alfa AF: 0.779 Hom.: 8145

Bravo AF: 0.763

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.25
PhyloP100		-0.21
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: rs7705319; hg19: chr5-133540070;