19-52190204-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000454220.7(PPP2R1A):c.108A>C(p.Arg36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,547,534 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 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 ( 96 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 56 hom. )

Consequence

PPP2R1A
ENST00000454220.7 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.295

Publications

2 publications found

Variant links:

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]

PPP2R1A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Houge-Janssens syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Illumina

PPP2R1A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000454220.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019791424).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454220.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R1A	NM_014225.6	MANE Select	c.78+30A>C		intron	N/A	NP_055040.2
	PPP2R1A	NR_033500.2		n.123+30A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP2R1A	ENST00000454220.7	TSL:1	c.108A>C	p.Arg36Ser	missense	Exon 1 of 15	ENSP00000391905.3	C9J9C1
PPP2R1A	ENST00000322088.11	TSL:1 MANE Select	c.78+30A>C		intron	N/A	ENSP00000324804.6	P30153
PPP2R1A	ENST00000703398.1		c.78+30A>C		intron	N/A	ENSP00000515288.1	A0A994J3H1

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2804

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

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

GnomAD2 exomes

AF:

0.00399

AC:

593

AN:

148444

AF XY:

0.00324

show subpopulations

Gnomad AFR exome

AF:

0.0625

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000234

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.00183

AC:

2548

AN:

1395228

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1089

AN XY:

688216

show subpopulations

African (AFR)

AF:

0.0624

AC:

1944

AN:

31154

American (AMR)

AF:

0.00455

AC:

161

AN:

35414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24998

East Asian (EAS)

AF:

0.00

AC:

AN:

35218

South Asian (SAS)

AF:

0.000253

AC:

AN:

79132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48792

Middle Eastern (MID)

AF:

0.00405

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.000111

AC:

120

AN:

1076996

Other (OTH)

AF:

0.00484

AC:

280

AN:

57846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

129

257

386

514

643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0185

AC:

2812

AN:

152306

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1320

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0637

AC:

2650

AN:

41574

American (AMR)

AF:

0.00634

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68022

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

130

260

389

519

649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00841

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.33

CADD

Benign

1.2

(source)

DANN

Benign

0.78

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

PhyloP100

-0.29

PROVEAN

Benign

0.030

REVEL

Benign

0.064

Sift

Benign

0.094

Sift4G

Benign

0.13

PromoterAI

-0.044

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over