14-101882276-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001352913.2(PPP2R5C):c.570+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,602,094 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (116 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (124 hom.)
• Consequence: PPP2R5C NM_001352913.2 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.00002733
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-101882276-C-T is Benign according to our data. Variant chr14-101882276-C-T is described in ClinVar as [Benign]. Clinvar id is 776862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5C	NM_001352913.2	c.570+5C>T		splice_donor_5th_base_variant, intron_variant		ENST00000694906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.570+5C>T		splice_donor_5th_base_variant, intron_variant			NM_001352913.2	P3

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3222 AN: 152086 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00564 AC: 1386 AN: 245646 Hom.: 42 AF XY: 0.00391 AC XY: 519 AN XY: 132720

Gnomad AFR exome AF: 0.0767

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.000386

Gnomad SAS exome AF: 0.000307

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00301

GnomAD4 exome AF: 0.00227 AC: 3291 AN: 1449890 Hom.: 124 Cov.: 29 AF XY: 0.00199 AC XY: 1435 AN XY: 721632

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.0000771

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000423

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000843

Gnomad4 OTH exome AF: 0.00450

GnomAD4 genome AF: 0.0213 AC: 3239 AN: 152204 Hom.: 116 Cov.: 33 AF XY: 0.0200 AC XY: 1488 AN XY: 74430

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.00478

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00988 Hom.: 24

Bravo AF: 0.0240

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.2
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.010
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: rs76972353; hg19: chr14-102348613;