rs9824246

Positions:

• chr3-73053574-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174907.4(PPP4R2):​c.288-5463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 152,166 control chromosomes in the GnomAD database, including 603 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 0.074 (603 hom., cov: 31)
• Consequence: PPP4R2 NM_174907.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

Genes affected

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

PPP4R2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R2	NM_174907.4	c.288-5463A>G		intron_variant		ENST00000356692.10	NP_777567.1
PPP4R2	NM_001318026.2	c.174-5463A>G		intron_variant			NP_001304955.1
PPP4R2	NM_001318025.2	c.117-5463A>G		intron_variant			NP_001304954.1
PPP4R2	NM_001318027.2	c.-164-5463A>G		intron_variant			NP_001304956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP4R2	ENST00000356692.10	c.288-5463A>G		intron_variant		1	NM_174907.4	ENSP00000349124.5

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11311 AN: 152048 Hom.: 602 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0744 AC: 11320 AN: 152166 Hom.: 603 Cov.: 31 AF XY: 0.0728 AC XY: 5419 AN XY: 74414

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0815

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.0220

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0512 Hom.: 417

Bravo AF: 0.0823

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.28

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: rs9824246; hg19: chr3-73102725;