Genetic Variant PPP2R1A:c.79-5757T>C (chr19-52196187-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014225.6(PPP2R1A):c.79-5757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 149,278 control chromosomes in the GnomAD database, including 51,784 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 0.84 ( 51784 hom., cov: 32)

Consequence

PPP2R1A
NM_014225.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

7 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: Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P

PPP2R1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014225.6. 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.79-5757T>C		intron	N/A	NP_055040.2
	PPP2R1A	NR_033500.2		n.124-5757T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R1A	ENST00000322088.11	TSL:1 MANE Select	c.79-5757T>C	intron	N/A	ENSP00000324804.6	P30153
PPP2R1A	ENST00000454220.7	TSL:1	c.199-5757T>C	intron	N/A	ENSP00000391905.3	C9J9C1
PPP2R1A	ENST00000703398.1		c.79-5757T>C	intron	N/A	ENSP00000515288.1	A0A994J3H1

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

124951

AN:

149164

Hom.:

51735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.918

Gnomad AMI

AF:

0.850

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.808

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.836

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.821

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

GnomAD4 genome

AF:

0.838

AC:

125053

AN:

149278

Hom.:

51784

Cov.:

AF XY:

0.835

AC XY:

60902

AN XY:

72958

show subpopulations

African (AFR)

AF:

0.918

AC:

37867

AN:

41260

American (AMR)

AF:

0.705

AC:

10437

AN:

14814

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

2727

AN:

3376

East Asian (EAS)

AF:

0.758

AC:

3909

AN:

5156

South Asian (SAS)

AF:

0.836

AC:

3958

AN:

4736

European-Finnish (FIN)

AF:

0.818

AC:

8495

AN:

10390

Middle Eastern (MID)

AF:

0.782

AC:

222

AN:

284

European-Non Finnish (NFE)

AF:

0.829

AC:

55000

AN:

66324

Other (OTH)

AF:

0.821

AC:

1688

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1122

2244

3366

4488

5610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.879

Hom.:

106048

Bravo

AF:

0.880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.58

(source)

DANN

Benign

0.59

PhyloP100

-1.7

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over