rs4802905

chr19-52220842-T-C

Variant summary

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

The NM_014225.6(PPP2R1A):c.1364-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,031,006 control chromosomes in the GnomAD database, including 13,322 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 0.19 (3394 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9928 hom.)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 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 constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R1A	NM_014225.6	c.1364-137T>C		intron_variant		ENST00000322088.11
PPP2R1A	NM_001363656.2	c.827-137T>C		intron_variant
PPP2R1A	NR_033500.2	n.1308-137T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.1364-137T>C		intron_variant		1	NM_014225.6	P4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28457 AN: 151962 Hom.: 3381 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.136 AC: 119471 AN: 878926 Hom.: 9928 AF XY: 0.136 AC XY: 60592 AN XY: 445740

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.0981

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.187 AC: 28514 AN: 152080 Hom.: 3394 Cov.: 32 AF XY: 0.188 AC XY: 13984 AN XY: 74342

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.181

Alfa AF: 0.141 Hom.: 414

Bravo AF: 0.200

Asia WGS AF: 0.267 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.0
Dann	Benign	0.67

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: rs4802905; hg19: chr19-52724095; COSMIC: COSV59043211; COSMIC: COSV59043211;