4-6384955-T-G

Position:

• chr4-6384955-T-G

Variant summary

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

The NM_020416.4(PPP2R2C):​c.71-3861A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 661,658 control chromosomes in the GnomAD database, including 84,122 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 0.43 (15932 hom., cov: 32)
  • Exomes 𝑓: 0.51 (68190 hom.)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2C	NM_020416.4	c.71-3861A>C		intron_variant		ENST00000382599.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.71-3861A>C		intron_variant		1	NM_020416.4	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65556 AN: 151918 Hom.: 15919 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.511 AC: 260490 AN: 509620 Hom.: 68190 AF XY: 0.512 AC XY: 122345 AN XY: 239088

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.431 AC: 65589 AN: 152038 Hom.: 15932 Cov.: 32 AF XY: 0.435 AC XY: 32338 AN XY: 74320

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.441

Alfa AF: 0.477 Hom.: 7822

Bravo AF: 0.426

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.53

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: rs875864; hg19: chr4-6386682;