dbSNP rs10491322: PPP2CA:c.*3323T>C (chr5-134194449-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002715.4(PPP2CA):c.*3323T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 152,288 control chromosomes in the GnomAD database, including 795 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 0.095 ( 795 hom., cov: 32)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

PPP2CA
NM_002715.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

Publications

10 publications found

Variant links:

Genes affected

PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A 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. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

PPP2CA Gene-Disease associations (from GenCC):

Houge-Janssens syndrome 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

PPP2CA links:

ENSG00000272772 (HGNC:):

ENSG00000272772 links:

Genome browser will be placed here

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=-0.69).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPP2CA	NM_002715.4 link	c.*3323T>C	3_prime_UTR_variant	Exon 7 of 7	ENST00000481195.6	NP_002706.1	P67775-1B3KUN1
PPP2CA	NR_149151.2 link	n.4508T>C	non_coding_transcript_exon_variant	Exon 7 of 7
PPP2CA	NM_001355019.2 link	c.*3323T>C	3_prime_UTR_variant	Exon 7 of 7		NP_001341948.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP2CA	ENST00000481195.6 link	c.*3323T>C	3_prime_UTR_variant	Exon 7 of 7	1	NM_002715.4	ENSP00000418447.1	P67775-1
ENSG00000272772	ENST00000519718.2 link	c.103-20427T>C	intron_variant	Intron 1 of 5	5		ENSP00000430774.2	E5RI56
PPP2CA	ENST00000703354.2 link	c.*3323T>C	3_prime_UTR_variant	Exon 7 of 7			ENSP00000515268.1	A0A8V8TRB3

Frequencies

GnomAD3 genomes

AF:

0.0953

AC:

14494

AN:

152156

Hom.:

790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.0544

Gnomad SAS

AF:

0.0983

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0953

AC:

14513

AN:

152274

Hom.:

795

Cov.:

AF XY:

0.101

AC XY:

7501

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.118

AC:

4895

AN:

41530

American (AMR)

AF:

0.153

AC:

2343

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3470

East Asian (EAS)

AF:

0.0539

AC:

280

AN:

5192

South Asian (SAS)

AF:

0.0986

AC:

476

AN:

4830

European-Finnish (FIN)

AF:

0.141

AC:

1490

AN:

10604

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0651

AC:

4427

AN:

68022

Other (OTH)

AF:

0.116

AC:

246

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

659

1318

1978

2637

3296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0856

Hom.:

375

Bravo

AF:

0.0984

Asia WGS

AF:

0.0970

AC:

337

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

(source)

DANN

Benign

0.89

PhyloP100

0.27

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over