rs2720208

Variant names:

• chr14-101911437-A-G
• rs2720208
• NM_001352913.2:c.1419-964A>G

Variant summary

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

The NM_001352913.2(PPP2R5C):​c.1419-964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,112 control chromosomes in the GnomAD database, including 13,664 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 0.36 (13664 hom., cov: 32)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 4 publications found

Genes affected

PPP2R5C (HGNC:9311): (protein phosphatase 2 regulatory subunit B'gamma) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5C Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352913.2. 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
	PPP2R5C	NM_001352913.2	MANE Select	c.1419-964A>G		intron	N/A	NP_001339842.1
	PPP2R5C	NM_001161725.2		c.1347-964A>G		intron	N/A	NP_001155197.1
	PPP2R5C	NM_001352914.2		c.1434-964A>G		intron	N/A	NP_001339843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	ENST00000694906.1	MANE Select	c.1419-964A>G		intron	N/A	ENSP00000511581.1
	PPP2R5C	ENST00000334743.9	TSL:1	c.1254-964A>G		intron	N/A	ENSP00000333905.4
	PPP2R5C	ENST00000350249.7	TSL:1	c.1254-964A>G		intron	N/A	ENSP00000262239.5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54009 AN: 151994 Hom.: 13625 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.356 AC: 54102 AN: 152112 Hom.: 13664 Cov.: 32 AF XY: 0.352 AC XY: 26139 AN XY: 74362

African (AFR) AF: 0.725 AC: 30076 AN: 41474

American (AMR) AF: 0.241 AC: 3687 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1598 AN: 5170

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10590

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13365 AN: 67992

Other (OTH) AF: 0.339 AC: 715 AN: 2110

Alfa AF: 0.265 Hom.: 2742

Bravo AF: 0.376

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.32
PhyloP100		-2.0
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: rs2720208; hg19: chr14-102377774;