rs16838698

Positions:

• chr4-6384312-A-C
• chr4-6384312-A-G
• chr4-6384312-A-T

Variant summary

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

The NM_020416.4(PPP2R2C):​c.71-3218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 985,158 control chromosomes in the GnomAD database, including 209,299 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 0.57 (27047 hom., cov: 34)
  • Exomes 𝑓: 0.66 (182252 hom.)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2C	NM_020416.4	c.71-3218T>G		intron_variant		ENST00000382599.9	NP_065149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.71-3218T>G		intron_variant		1	NM_020416.4	ENSP00000372042	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86633 AN: 152068 Hom.: 27039 Cov.: 34

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.659 AC: 548803 AN: 832972 Hom.: 182252 Cov.: 34 AF XY: 0.659 AC XY: 253321 AN XY: 384660

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.569 AC: 86659 AN: 152186 Hom.: 27047 Cov.: 34 AF XY: 0.574 AC XY: 42749 AN XY: 74420

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.580

Alfa AF: 0.651 Hom.: 43930

Bravo AF: 0.561

Asia WGS AF: 0.605 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.58

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: rs16838698; hg19: chr4-6386039;