rs9291117

Variant names:

• chr4-6445880-G-A
• rs9291117
• NM_020416.4:c.70+26280C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP2R2C	NM_020416.4	c.70+26280C>T		intron_variant	Intron 1 of 8	ENST00000382599.9	NP_065149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.70+26280C>T		intron_variant	Intron 1 of 8	1	NM_020416.4	ENSP00000372042.4

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

African (AFR) AF: 0.167 AC: 6916 AN: 41494

American (AMR) AF: 0.0814 AC: 1245 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0684 AC: 237 AN: 3466

East Asian (EAS) AF: 0.0645 AC: 334 AN: 5180

South Asian (SAS) AF: 0.0991 AC: 477 AN: 4814

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10590

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9683 AN: 67970

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.137 Hom.: 6816

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
PhyloP100		-0.24
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: rs9291117; hg19: chr4-6447607;