rs875579

Variant names:

• chr4-6561216-G-A
• rs875579
• NM_001206994.2:c.-59+2344C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-6561216-G-A
• chr4-6561216-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-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 rank	MANE	Protein	UniProt
PPP2R2C	NM_001206994.2	c.-59+2344C>T		intron_variant	Intron 1 of 9		NP_001193923.1
PPP2R2C	XM_047415891.1	c.-396+2344C>T		intron_variant	Intron 1 of 8		XP_047271847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000506140.5	c.-59+2344C>T		intron_variant	Intron 1 of 9	2		ENSP00000423649.1

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

African (AFR) AF: 0.0717 AC: 2977 AN: 41498

American (AMR) AF: 0.312 AC: 4768 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1192 AN: 3460

East Asian (EAS) AF: 0.527 AC: 2713 AN: 5152

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4826

European-Finnish (FIN) AF: 0.471 AC: 4971 AN: 10562

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25178 AN: 67956

Other (OTH) AF: 0.288 AC: 607 AN: 2108

Alfa AF: 0.334 Hom.: 3481

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
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs875579; hg19: chr4-6562943;