rs9291117

Positions:

• chr4-6445880-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020416.4(PPP2R2C):​c.70+26280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,130 control chromosomes in the GnomAD database, including 1,488 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 0.14 (1488 hom., cov: 32)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

Genes affected

PPP2R2C (HGNC:9306): (protein phosphatase 2 regulatory subunit Bgamma) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2C	NM_020416.4	c.70+26280C>T		intron_variant		ENST00000382599.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.70+26280C>T		intron_variant		1	NM_020416.4	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20832 AN: 152012 Hom.: 1489 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0684

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.137 AC: 20843 AN: 152130 Hom.: 1488 Cov.: 32 AF XY: 0.134 AC XY: 9936 AN XY: 74374

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0684

Gnomad4 EAS AF: 0.0645

Gnomad4 SAS AF: 0.0991

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.120

Alfa AF: 0.135 Hom.: 3194

Bravo AF: 0.134

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.55

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: rs9291117; hg19: chr4-6447607;