rs4689440

Variant names:

• chr4-6419679-G-A
• rs4689440
• NM_020416.4:c.71-38585C>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.71-38585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,018 control chromosomes in the GnomAD database, including 4,377 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 0.22 (4377 hom., cov: 32)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2C	NM_020416.4	c.71-38585C>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.71-38585C>T		intron_variant	Intron 1 of 8	1	NM_020416.4	ENSP00000372042.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34061 AN: 151900 Hom.: 4367 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.224 AC: 34086 AN: 152018 Hom.: 4377 Cov.: 32 AF XY: 0.231 AC XY: 17148 AN XY: 74296

African (AFR) AF: 0.137 AC: 5681 AN: 41468

American (AMR) AF: 0.363 AC: 5534 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 897 AN: 3472

East Asian (EAS) AF: 0.178 AC: 916 AN: 5158

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4812

European-Finnish (FIN) AF: 0.338 AC: 3579 AN: 10574

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15449 AN: 67956

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.239 Hom.: 6902

Bravo AF: 0.226

Asia WGS AF: 0.272 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.41
PhyloP100		-0.68
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: rs4689440; hg19: chr4-6421406;