rs7704116

Positions:

• chr5-134216763-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.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

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=-0.93).
• 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/exons	MANE	Protein	UniProt
PPP2CA	NM_002715.4	c.102+8997G>A		intron_variant		ENST00000481195.6	NP_002706.1
PPP2CA	NM_001355019.2	c.-94+8446G>A		intron_variant			NP_001341948.1
PPP2CA	NR_149151.2	n.346+8446G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2CA	ENST00000481195.6	c.102+8997G>A		intron_variant		1	NM_002715.4	ENSP00000418447	P4

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0747 Hom.: 791

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

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: rs7704116; hg19: chr5-133552454;