Genetic Variant PPP2R3C:c.1174-10dupT (chr14-35085787-G-GA) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_017917.4(PPP2R3C):c.1174-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,537,448 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 2 hom. )

Consequence

PPP2R3C
NM_017917.4 intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0310

Variant links:

Genes affected

PPP2R3C (HGNC:17485): (protein phosphatase 2 regulatory subunit B''gamma) This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PPP2R3C links:

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

FAM177A1 links:

LOC101927178 (HGNC:):

LOC101927178 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 14-35085787-G-GA is Benign according to our data. Variant chr14-35085787-G-GA is described in ClinVar as [Benign]. Clinvar id is 3039479.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00259 (390/150464) while in subpopulation AFR AF = 0.00872 (358/41064). AF 95% confidence interval is 0.00797. There are 2 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3C	NM_017917.4 link	c.1174-10dupT		intron_variant	Intron 12 of 12	ENST00000261475.10	NP_060387.2	Q969Q6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10 link	c.1174-10_1174-9insT		intron_variant	Intron 12 of 12	1	NM_017917.4	ENSP00000261475.5		Q969Q6-1

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

390

AN:

150352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00874

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000968

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.000970

GnomAD2 exomes

AF:

0.00241

AC:

431

AN:

179080

AF XY:

0.00229

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.00165

Gnomad FIN exome

AF:

0.00263

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.000952

GnomAD4 exome

AF:

0.000989

AC:

1372

AN:

1386984

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

635

AN XY:

690408

show subpopulations

Gnomad4 AFR exome

AF:

0.00900

AC:

273

AN:

30350

Gnomad4 AMR exome

AF:

0.00163

AC:

AN:

36240

Gnomad4 ASJ exome

AF:

0.000662

AC:

AN:

24170

Gnomad4 EAS exome

AF:

0.000598

AC:

AN:

38446

Gnomad4 SAS exome

AF:

0.00107

AC:

AN:

78626

Gnomad4 FIN exome

AF:

0.00106

AC:

AN:

50060

Gnomad4 NFE exome

AF:

0.000745

AC:

795

AN:

1066426

Gnomad4 Remaining exome

AF:

0.00115

AC:

AN:

57190

Heterozygous variant carriers

169

338

506

675

844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00259

AC:

390

AN:

150464

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

172

AN XY:

73396

show subpopulations

Gnomad4 AFR

AF:

0.00872

AC:

0.0087181

AN:

0.0087181

Gnomad4 AMR

AF:

0.00139

AC:

0.00139018

AN:

0.00139018

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000970

AC:

0.000970497

AN:

0.000970497

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000592

AC:

0.0000592435

AN:

0.0000592435

Gnomad4 OTH

AF:

0.000960

AC:

0.000959693

AN:

0.000959693

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome 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

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00288

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R3C-related disorder

Benign:1

Nov 25, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over