chr3-73053574-A-G

Variant names:

• chr3-73053574-A-G
• rs9824246
• NM_174907.4:c.288-5463A>G

Variant summary

Our verdict is Benign. The variant received -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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP4R2	NM_174907.4	c.288-5463A>G		intron_variant	Intron 3 of 8	ENST00000356692.10	NP_777567.1
PPP4R2	NM_001318026.2	c.174-5463A>G		intron_variant	Intron 3 of 8		NP_001304955.1
PPP4R2	NM_001318025.2	c.117-5463A>G		intron_variant	Intron 2 of 7		NP_001304954.1
PPP4R2	NM_001318027.2	c.-164-5463A>G		intron_variant	Intron 2 of 7		NP_001304956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP4R2	ENST00000356692.10	c.288-5463A>G		intron_variant	Intron 3 of 8	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

African (AFR) AF: 0.143 AC: 5915 AN: 41480

American (AMR) AF: 0.0815 AC: 1245 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5176

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4830

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0433 AC: 2942 AN: 67990

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0545 Hom.: 1148

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
Mutation Taster		=100/0	polymorphism (auto)

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;