NM_020416.4:c.70+33267A>C

Variant names:

• chr4-6438893-T-G
• rs16838844
• NM_020416.4:c.70+33267A>C

Variant summary

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

The NM_020416.4(PPP2R2C):​c.70+33267A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,998 control chromosomes in the GnomAD database, including 23,517 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 0.54 (23517 hom., cov: 32)
• Consequence: PPP2R2C NM_020416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020416.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2C	NM_020416.4	MANE Select	c.70+33267A>C		intron	N/A	NP_065149.2
	PPP2R2C	NM_001206994.2		c.50-57799A>C		intron	N/A	NP_001193923.1
	PPP2R2C	NM_001206995.2		c.50-57799A>C		intron	N/A	NP_001193924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2C	ENST00000382599.9	TSL:1 MANE Select	c.70+33267A>C		intron	N/A	ENSP00000372042.4
	PPP2R2C	ENST00000506140.5	TSL:2	c.50-57799A>C		intron	N/A	ENSP00000423649.1
	PPP2R2C	ENST00000507294.1	TSL:2	c.50-57799A>C		intron	N/A	ENSP00000425247.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82664 AN: 151880 Hom.: 23516 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.544 AC: 82685 AN: 151998 Hom.: 23517 Cov.: 32 AF XY: 0.531 AC XY: 39428 AN XY: 74266

African (AFR) AF: 0.457 AC: 18937 AN: 41446

American (AMR) AF: 0.420 AC: 6406 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2050 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1541 AN: 5162

South Asian (SAS) AF: 0.483 AC: 2326 AN: 4814

European-Finnish (FIN) AF: 0.496 AC: 5239 AN: 10564

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44163 AN: 67978

Other (OTH) AF: 0.550 AC: 1159 AN: 2106

Alfa AF: 0.593 Hom.: 9108

Bravo AF: 0.531

Asia WGS AF: 0.360 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.9
DANN	Benign	0.74
PhyloP100		-0.029
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: rs16838844; hg19: chr4-6440620;