rs7251605

chr19-52208067-G-Achr19-52208067-G-C

Variant summary

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

The NM_014225.6(PPP2R1A):c.270+2004G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,170 control chromosomes in the GnomAD database, including 4,382 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 0.23 (4382 hom., cov: 32)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R1A	NM_014225.6	c.270+2004G>A		intron_variant		ENST00000322088.11
PPP2R1A	NM_001363656.2	c.-268+2004G>A		intron_variant
PPP2R1A	NR_033500.2	n.215-3193G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.270+2004G>A		intron_variant		1	NM_014225.6	P4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34900 AN: 152052 Hom.: 4373 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34942 AN: 152170 Hom.: 4382 Cov.: 32 AF XY: 0.226 AC XY: 16782 AN XY: 74394

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.220

Alfa AF: 0.214 Hom.: 4845

Bravo AF: 0.236

Asia WGS AF: 0.0820 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.55

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: rs7251605; hg19: chr19-52711320;