rs13434456

Positions:

• chr4-6412671-G-A

Variant summary

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

The NM_020416.4(PPP2R2C):​c.71-31577C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 5,022 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 0.25 (5022 hom., cov: 33)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2C	NM_020416.4	c.71-31577C>T		intron_variant		ENST00000382599.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.71-31577C>T		intron_variant		1	NM_020416.4	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37688 AN: 151956 Hom.: 5012 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.248 AC: 37723 AN: 152074 Hom.: 5022 Cov.: 33 AF XY: 0.253 AC XY: 18832 AN XY: 74334

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.264

Alfa AF: 0.245 Hom.: 6626

Bravo AF: 0.254

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.55

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: rs13434456; hg19: chr4-6414398;