Variant 14-35085787-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000261475.10(PPP2R3C):c.1174-10_1174-9insT variant causes a splice polypyrimidine tract, 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
ENST00000261475.10 splice_polypyrimidine_tract, 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:

LOC101927178 (HGNC:):

LOC101927178 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R3C	NM_017917.4 linkuse as main transcript	c.1174-10_1174-9insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261475.10	NP_060387.2
LOC101927178	NR_110415.1 linkuse as main transcript	n.479+4237dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10 linkuse as main transcript	c.1174-10_1174-9insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017917.4	ENSP00000261475	P1	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

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

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000662

Gnomad4 EAS exome

AF:

0.000598

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.000745

Gnomad4 OTH exome

AF:

0.00115

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

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000970

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.000960

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

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

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