rs114390941

chr19-52190256-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

The ENST00000454220.7(PPP2R1A):c.160T>G(p.Phe54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,469,822 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.018 (94 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (54 hom.)
• Consequence: PPP2R1A ENST00000454220.7 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.799

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 -11 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PPP2R1A
• BP4: Computational evidence support a benign effect (MetaRNN=0.0024425983).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R1A	NM_014225.6	c.78+82T>G		intron_variant		ENST00000322088.11
PPP2R1A	NR_033500.2	n.123+82T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.78+82T>G		intron_variant		1	NM_014225.6	P4

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2796 AN: 152208 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00634

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00393 AC: 507 AN: 129066 Hom.: 18 AF XY: 0.00335 AC XY: 234 AN XY: 69854

Gnomad AFR exome AF: 0.0634

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000429

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000192

Gnomad OTH exome AF: 0.00274

GnomAD4 exome AF: 0.00179 AC: 2353 AN: 1317496 Hom.: 54 Cov.: 20 AF XY: 0.00157 AC XY: 1025 AN XY: 651004

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.00448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.00476

GnomAD4 genome AF: 0.0184 AC: 2804 AN: 152326 Hom.: 94 Cov.: 33 AF XY: 0.0177 AC XY: 1319 AN XY: 74490

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0106 Hom.: 17

Bravo AF: 0.0205

ExAC AF: 0.00435 AC: 141

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	16
Dann	Benign	0.97
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.017
Sift	Benign	0.079	T
Sift4G	Benign	0.072	T
MVP		0.57
ClinPred		0.035	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs114390941; hg19: chr19-52693509;