chr19-52220677-C-T

Position:

• chr19-52220677-C-T

Variant summary

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

The NM_014225.6(PPP2R1A):​c.1364-302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,006 control chromosomes in the GnomAD database, including 2,478 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 0.18 (2478 hom., cov: 32)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

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 = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R1A	NM_014225.6	c.1364-302C>T		intron_variant		ENST00000322088.11
PPP2R1A	NM_001363656.2	c.827-302C>T		intron_variant
PPP2R1A	NR_033500.2	n.1308-302C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.1364-302C>T		intron_variant		1	NM_014225.6	P4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26763 AN: 151888 Hom.: 2469 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.176 AC: 26828 AN: 152006 Hom.: 2478 Cov.: 32 AF XY: 0.175 AC XY: 13032 AN XY: 74280

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.161

Alfa AF: 0.150 Hom.: 2415

Bravo AF: 0.176

Asia WGS AF: 0.131 AC: 458 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	0.76
DANN	Benign	0.48

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: rs8100500; hg19: chr19-52723930;