rs7142002

Variant names:

• chr14-101894408-T-C
• rs7142002
• NM_001352913.2:c.964-99T>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.964-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,139,104 control chromosomes in the GnomAD database, including 3,792 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 0.10 (1283 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2509 hom.)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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.964-99T>C		intron	N/A	NP_001339842.1
	PPP2R5C	NM_001161725.2		c.892-99T>C		intron	N/A	NP_001155197.1
	PPP2R5C	NM_001352914.2		c.979-99T>C		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.964-99T>C		intron	N/A	ENSP00000511581.1
	PPP2R5C	ENST00000334743.9	TSL:1	c.799-99T>C		intron	N/A	ENSP00000333905.4
	PPP2R5C	ENST00000350249.7	TSL:1	c.799-99T>C		intron	N/A	ENSP00000262239.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15794 AN: 152130 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0951

GnomAD4 exome AF: 0.0605 AC: 59702 AN: 986856 Hom.: 2509 AF XY: 0.0583 AC XY: 29548 AN XY: 506694

African (AFR) AF: 0.219 AC: 5212 AN: 23800

American (AMR) AF: 0.0599 AC: 2382 AN: 39738

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 1784 AN: 22380

East Asian (EAS) AF: 0.147 AC: 5392 AN: 36578

South Asian (SAS) AF: 0.0260 AC: 1891 AN: 72822

European-Finnish (FIN) AF: 0.0279 AC: 1409 AN: 50550

Middle Eastern (MID) AF: 0.0935 AC: 451 AN: 4826

European-Non Finnish (NFE) AF: 0.0549 AC: 37963 AN: 691836

Other (OTH) AF: 0.0726 AC: 3218 AN: 44326

GnomAD4 genome AF: 0.104 AC: 15819 AN: 152248 Hom.: 1283 Cov.: 32 AF XY: 0.100 AC XY: 7448 AN XY: 74440

African (AFR) AF: 0.217 AC: 9002 AN: 41520

American (AMR) AF: 0.0758 AC: 1158 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.162 AC: 841 AN: 5180

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4824

European-Finnish (FIN) AF: 0.0264 AC: 281 AN: 10628

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0562 AC: 3822 AN: 68032

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0738 Hom.: 2489

Bravo AF: 0.115

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		-0.23
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: rs7142002; hg19: chr14-102360745; COSMIC: COSV58269359; COSMIC: COSV58269359;