NM_001352913.2:c.460-6848T>C

Variant names:

• chr14-101875313-T-C
• rs1677999
• NM_001352913.2:c.460-6848T>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.460-6848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,046 control chromosomes in the GnomAD database, including 13,389 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 0.37 (13389 hom., cov: 32)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.460-6848T>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.460-6848T>C		intron_variant	Intron 4 of 15		NM_001352913.2	ENSP00000511581.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56819 AN: 151928 Hom.: 13345 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.374 AC: 56923 AN: 152046 Hom.: 13389 Cov.: 32 AF XY: 0.365 AC XY: 27108 AN XY: 74348

African (AFR) AF: 0.657 AC: 27244 AN: 41454

American (AMR) AF: 0.407 AC: 6216 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1352 AN: 5162

South Asian (SAS) AF: 0.295 AC: 1424 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1269 AN: 10586

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17003 AN: 67960

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.293 Hom.: 12106

Bravo AF: 0.409

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.37
PhyloP100		-1.9
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: rs1677999; hg19: chr14-102341650;