rs10431745

Variant names:

• chr14-101836035-A-G
• rs10431745
• NM_001352913.2:c.260-20651A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352913.2(PPP2R5C):​c.260-20651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 597,446 control chromosomes in the GnomAD database, including 2,172 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 0.092 (756 hom., cov: 33)
  • Exomes 𝑓: 0.070 (1416 hom.)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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]

ENSG00000256705 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.260-20651A>G		intron_variant	Intron 3 of 15	ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.260-20651A>G		intron_variant	Intron 3 of 15		NM_001352913.2	ENSP00000511581.1

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13976 AN: 152194 Hom.: 752 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0700 AC: 31167 AN: 445134 Hom.: 1416 AF XY: 0.0665 AC XY: 15557 AN XY: 234076

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.0428

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0654

Gnomad4 NFE exome AF: 0.0671

Gnomad4 OTH exome AF: 0.0776

GnomAD4 genome AF: 0.0920 AC: 14015 AN: 152312 Hom.: 756 Cov.: 33 AF XY: 0.0908 AC XY: 6766 AN XY: 74488

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.0904

Alfa AF: 0.0883 Hom.: 124

Bravo AF: 0.103

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.6
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs10431745; hg19: chr14-102302372;