rs7704116

Variant names:

• chr5-134216763-C-T
• rs7704116
• NM_002715.4:c.102+8997G>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.102+8997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,042 control chromosomes in the GnomAD database, including 876 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 0.099 (876 hom., cov: 31)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.102+8997G>A		intron_variant	Intron 1 of 6	ENST00000481195.6	NP_002706.1
PPP2CA	NM_001355019.2	c.-94+8446G>A		intron_variant	Intron 1 of 6		NP_001341948.1
PPP2CA	NR_149151.2	n.346+8446G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.102+8997G>A		intron_variant	Intron 1 of 6	1	NM_002715.4	ENSP00000418447.1
ENSG00000272772	ENST00000519718.2	c.102+8997G>A		intron_variant	Intron 1 of 5	5		ENSP00000430774.2
ENSG00000273345	ENST00000703317.1	n.*74-10632G>A		intron_variant	Intron 4 of 9			ENSP00000515260.1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15050 AN: 151924 Hom.: 869 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.0992 AC: 15078 AN: 152042 Hom.: 876 Cov.: 31 AF XY: 0.105 AC XY: 7790 AN XY: 74344

African (AFR) AF: 0.131 AC: 5429 AN: 41462

American (AMR) AF: 0.155 AC: 2372 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.0536 AC: 277 AN: 5170

South Asian (SAS) AF: 0.0976 AC: 470 AN: 4814

European-Finnish (FIN) AF: 0.140 AC: 1477 AN: 10550

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.0653 AC: 4441 AN: 68000

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.0803 Hom.: 1608

Bravo AF: 0.103

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		-0.23
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: rs7704116; hg19: chr5-133552454;