dbSNP rs2749907: PPP2R5C:c.460-2805G>A (chr14-101879356-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001352913.2(PPP2R5C):c.460-2805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,604 control chromosomes in the GnomAD database, including 12,115 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 0.35 ( 12100 hom., cov: 32)

Exomes 𝑓: 0.21 ( 15 hom. )

Consequence

PPP2R5C
NM_001352913.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

Publications

3 publications found

Variant links:

Genes affected

PPP2R5C (HGNC:9311): (protein phosphatase 2 regulatory subunit B'gamma) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5C Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PPP2R5C 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2 link	c.460-2805G>A		intron_variant	Intron 4 of 15	ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1 link	c.460-2805G>A		intron_variant	Intron 4 of 15		NM_001352913.2	ENSP00000511581.1		A0A8Q3WKR3

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53252

AN:

152014

Hom.:

12069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.215

AC:

101

AN:

470

Hom.:

Cov.:

AF XY:

0.216

AC XY:

AN XY:

356

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.212

AC:

AN:

400

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.351

AC:

53330

AN:

152134

Hom.:

12100

Cov.:

AF XY:

0.347

AC XY:

25773

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.652

AC:

27059

AN:

41504

American (AMR)

AF:

0.239

AC:

3653

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1008

AN:

3472

East Asian (EAS)

AF:

0.276

AC:

1423

AN:

5162

South Asian (SAS)

AF:

0.269

AC:

1295

AN:

4818

European-Finnish (FIN)

AF:

0.261

AC:

2769

AN:

10592

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15113

AN:

67976

Other (OTH)

AF:

0.338

AC:

715

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1536

3072

4609

6145

7681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.252

Hom.:

17259

Bravo

AF:

0.364

Asia WGS

AF:

0.275

AC:

956

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.62

PhyloP100

-0.79

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