rs1677999

chr14-101875313-T-Cchr14-101875313-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PPP2R5C	NM_001352913.2	c.460-6848T>C		intron_variant		ENST00000694906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.460-6848T>C		intron_variant			NM_001352913.2	P3

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

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.385

Alfa AF: 0.278 Hom.: 8360

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

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: rs1677999; hg19: chr14-102341650;