rs10937739

chr4-6507685-T-Cchr4-6507685-T-G

Variant summary

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

The NM_001206994.2(PPP2R2C):c.49+27586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,128 control chromosomes in the GnomAD database, including 16,743 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 0.45 (16743 hom., cov: 33)
• Consequence: PPP2R2C NM_001206994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2C	NM_001206994.2	c.49+27586A>G		intron_variant
PPP2R2C	NM_001206995.2	c.49+27586A>G		intron_variant
PPP2R2C	XM_047415891.1	c.-396+55875A>G		intron_variant
PPP2R2C	XM_047415892.1	c.-396+21337A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2C	ENST00000506140.5	c.49+27586A>G		intron_variant		2
PPP2R2C	ENST00000507294.1	c.49+27586A>G		intron_variant		2
PPP2R2C	ENST00000314348.12	n.105+15758A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68908 AN: 152010 Hom.: 16722 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.453 AC: 68959 AN: 152128 Hom.: 16743 Cov.: 33 AF XY: 0.462 AC XY: 34339 AN XY: 74356

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.495

Alfa AF: 0.480 Hom.: 29819

Bravo AF: 0.457

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.3
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10937739; hg19: chr4-6509412;