rs7145618

Variant names:

• chr14-101862761-T-C
• rs7145618
• NM_001352913.2:c.459+5876T>C

Variant summary

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

The NM_001352913.2(PPP2R5C):​c.459+5876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 151,006 control chromosomes in the GnomAD database, including 394 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 0.061 (394 hom., cov: 32)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.459+5876T>C		intron_variant	Intron 4 of 15	ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.459+5876T>C		intron_variant	Intron 4 of 15		NM_001352913.2	ENSP00000511581.1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9147 AN: 150898 Hom.: 388 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0803

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

GnomAD4 genome AF: 0.0607 AC: 9173 AN: 151006 Hom.: 394 Cov.: 32 AF XY: 0.0603 AC XY: 4452 AN XY: 73860

African (AFR) AF: 0.0370 AC: 1506 AN: 40682

American (AMR) AF: 0.141 AC: 2152 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 400 AN: 3448

East Asian (EAS) AF: 0.154 AC: 799 AN: 5188

South Asian (SAS) AF: 0.0348 AC: 167 AN: 4802

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10598

Middle Eastern (MID) AF: 0.108 AC: 31 AN: 288

European-Non Finnish (NFE) AF: 0.0555 AC: 3760 AN: 67764

Other (OTH) AF: 0.0818 AC: 172 AN: 2102

Alfa AF: 0.0612 Hom.: 290

Bravo AF: 0.0734

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.89
PhyloP100		0.83
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: rs7145618; hg19: chr14-102329098;