Genetic Variant NM_020416.4:c.71-3861A>C (chr4-6384955-T-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_020416.4(PPP2R2C):c.71-3861A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 661,658 control chromosomes in the GnomAD database, including 84,122 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 0.43 ( 15932 hom., cov: 32)

Exomes 𝑓: 0.51 ( 68190 hom. )

Consequence

PPP2R2C
NM_020416.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.725

Publications

7 publications found

Variant links:

Genes affected

PPP2R2C (HGNC:9306): (protein phosphatase 2 regulatory subunit Bgamma) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. 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 B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R2C 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2C	NM_020416.4 link	c.71-3861A>C		intron_variant	Intron 1 of 8	ENST00000382599.9	NP_065149.2	Q9Y2T4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000382599.9 link	c.71-3861A>C		intron_variant	Intron 1 of 8	1	NM_020416.4	ENSP00000372042.4		Q9Y2T4-1

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65556

AN:

151918

Hom.:

15919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.511

AC:

260490

AN:

509620

Hom.:

68190

AF XY:

0.512

AC XY:

122345

AN XY:

239088

show subpopulations

African (AFR)

AF:

0.164

AC:

1508

AN:

9194

American (AMR)

AF:

0.547

AC:

293

AN:

536

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1717

AN:

3254

East Asian (EAS)

AF:

0.579

AC:

1199

AN:

2072

South Asian (SAS)

AF:

0.532

AC:

5318

AN:

9988

European-Finnish (FIN)

AF:

0.482

AC:

AN:

170

Middle Eastern (MID)

AF:

0.513

AC:

518

AN:

1010

European-Non Finnish (NFE)

AF:

0.517

AC:

241569

AN:

466902

Other (OTH)

AF:

0.502

AC:

8286

AN:

16494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

5904

11808

17711

23615

29519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9416

18832

28248

37664

47080

<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:

0.431

AC:

65589

AN:

152038

Hom.:

15932

Cov.:

AF XY:

0.435

AC XY:

32338

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.193

AC:

7995

AN:

41486

American (AMR)

AF:

0.546

AC:

8349

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1800

AN:

3470

East Asian (EAS)

AF:

0.592

AC:

3062

AN:

5168

South Asian (SAS)

AF:

0.526

AC:

2530

AN:

4808

European-Finnish (FIN)

AF:

0.498

AC:

5257

AN:

10566

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34921

AN:

67946

Other (OTH)

AF:

0.441

AC:

928

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1747

3493

5240

6986

8733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.479

Hom.:

8793

Bravo

AF:

0.426

Asia WGS

AF:

0.539

AC:

1873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

(source)

DANN

Benign

0.53

PhyloP100

-0.72

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over