17-18898528-A-G

Position:

• chr17-18898528-A-G

Variant summary

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

The ENST00000268835.7(PRPSAP2):​c.584+8651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,976 control chromosomes in the GnomAD database, including 21,498 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 0.53 (21498 hom., cov: 31)
• Consequence: PRPSAP2 ENST00000268835.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

Genes affected

PRPSAP2 (HGNC:9467): (phosphoribosyl pyrophosphate synthetase associated protein 2) This gene encodes a protein that associates with the enzyme phosphoribosylpyrophosphate synthetase (PRS). PRS catalyzes the formation of phosphoribosylpyrophosphate which is a substrate for synthesis of purine and pyrimidine nucleotides, histidine, tryptophan and NAD. PRS exists as a complex with two catalytic subunits and two associated subunits. This gene encodes a non-catalytic associated subunit of PRS. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPSAP2	NM_002767.4	c.584+8651A>G		intron_variant		ENST00000268835.7	NP_002758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000268835.7	c.584+8651A>G		intron_variant		1	NM_002767.4	ENSP00000268835	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80298 AN: 151858 Hom.: 21481 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.529 AC: 80362 AN: 151976 Hom.: 21498 Cov.: 31 AF XY: 0.518 AC XY: 38497 AN XY: 74252

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.540

Alfa AF: 0.441 Hom.: 1536

Bravo AF: 0.539

Asia WGS AF: 0.376 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.25

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: rs8073436; hg19: chr17-18801841;