rs875579

Positions:

• chr4-6561216-G-A
• chr4-6561216-G-C

Variant summary

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

The NM_001206994.2(PPP2R2C):​c.-59+2344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,052 control chromosomes in the GnomAD database, including 8,147 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 0.29 (8147 hom., cov: 32)
• Consequence: PPP2R2C NM_001206994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2C	NM_001206994.2	c.-59+2344C>T		intron_variant
PPP2R2C	XM_047415891.1	c.-396+2344C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2C	ENST00000506140.5	c.-59+2344C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44461 AN: 151932 Hom.: 8151 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.292 AC: 44460 AN: 152052 Hom.: 8147 Cov.: 32 AF XY: 0.297 AC XY: 22057 AN XY: 74338

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.288

Alfa AF: 0.330 Hom.: 1863

Bravo AF: 0.273

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.050
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs875579; hg19: chr4-6562943;