14-35085787-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017917.4(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 (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (2 hom.)
• Consequence: PPP2R3C NM_017917.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0310

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]

LOC101927178 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 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 criteria_provided_single_submitter, 1 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 GnomAd at 2 AD,AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 390 AN: 150352 Hom.: 2 Cov.: 32

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.: 2 Cov.: 29 AF XY: 0.000920 AC XY: 635 AN XY: 690408

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.: 2 Cov.: 32 AF XY: 0.00234 AC XY: 172 AN XY: 73396

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: criteria provided, single submitter

Submissions by phenotype

PPP2R3C-related disorder Benign:1

Benign, criteria provided, single submitter

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

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

Other links and lift over

dbSNP: rs201794373; hg19: chr14-35554993;