19-52201708-T-C

Position:

• chr19-52201708-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.79-236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 517,322 control chromosomes in the GnomAD database, including 51,436 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 0.47 (17239 hom., cov: 31)
  • Exomes 𝑓: 0.43 (34197 hom.)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R1A	NM_014225.6	c.79-236T>C		intron_variant		ENST00000322088.11	NP_055040.2
PPP2R1A	NM_001363656.2	c.-460+14T>C		intron_variant			NP_001350585.1
PPP2R1A	NR_033500.2	n.124-236T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.79-236T>C		intron_variant		1	NM_014225.6	ENSP00000324804	P4

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70964 AN: 151778 Hom.: 17206 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.426 AC: 155617 AN: 365424 Hom.: 34197 Cov.: 2 AF XY: 0.423 AC XY: 81463 AN XY: 192490

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.468 AC: 71052 AN: 151898 Hom.: 17239 Cov.: 31 AF XY: 0.464 AC XY: 34427 AN XY: 74222

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.449

Alfa AF: 0.445 Hom.: 32167

Bravo AF: 0.466

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.54

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: rs10420138; hg19: chr19-52704961; COSMIC: COSV59044780; COSMIC: COSV59044780;