chrX-12821033-G-A

Position:

• chrX-12821033-G-A

Variant summary

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

The NM_002765.5(PRPS2):​c.864+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 111,345 control chromosomes in the GnomAD database, including 2,175 homozygotes. There are 6,472 hemizygotes in GnomAD. 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 0.20 (2175 hom., 6472 hem., cov: 23)
• Consequence: PRPS2 NM_002765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

Genes affected

PRPS2 (HGNC:9465): (phosphoribosyl pyrophosphate synthetase 2) This gene encodes a phosphoribosyl pyrophosphate synthetase that plays a central role in the synthesis of purines and pyrimidines. The encoded protein catalyzes the synthesis of 5-phosphoribosyl 1-pyrophosphate from ATP and D-ribose 5-phosphate. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPS2	NM_002765.5	c.864+230G>A		intron_variant		ENST00000380668.10
PRPS2	NM_001039091.3	c.873+230G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPS2	ENST00000380668.10	c.864+230G>A		intron_variant		1	NM_002765.5	P4
PRPS2	ENST00000398491.6	c.873+230G>A		intron_variant		1		A1
PRPS2	ENST00000461630.1	c.429+230G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 22312 AN: 111288 Hom.: 2173 Cov.: 23 AF XY: 0.192 AC XY: 6431 AN XY: 33532

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.0631

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.201 AC: 22367 AN: 111345 Hom.: 2175 Cov.: 23 AF XY: 0.193 AC XY: 6472 AN XY: 33599

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.209

Alfa AF: 0.139 Hom.: 7157

Bravo AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.094
DANN	Benign	0.66

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: rs7062536; hg19: chrX-12839152;