rs16838780

Variant names:

• chr4-6416058-T-C
• rs16838780
• NM_020416.4:c.71-34964A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020416.4(PPP2R2C):​c.71-34964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,100 control chromosomes in the GnomAD database, including 6,888 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 0.29 (6888 hom., cov: 33)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2C	NM_020416.4	c.71-34964A>G		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.71-34964A>G		intron_variant	Intron 1 of 8	1	NM_020416.4	ENSP00000372042.4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44409 AN: 151982 Hom.: 6889 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.292 AC: 44428 AN: 152100 Hom.: 6888 Cov.: 33 AF XY: 0.297 AC XY: 22054 AN XY: 74342

African (AFR) AF: 0.243 AC: 10095 AN: 41482

American (AMR) AF: 0.303 AC: 4631 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3166 AN: 5152

South Asian (SAS) AF: 0.335 AC: 1619 AN: 4830

European-Finnish (FIN) AF: 0.300 AC: 3175 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19716 AN: 67980

Other (OTH) AF: 0.287 AC: 606 AN: 2112

Alfa AF: 0.292 Hom.: 26718

Bravo AF: 0.287

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.82
PhyloP100		0.30
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: rs16838780; hg19: chr4-6417785;