Variant X-12819661-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002765.5(PRPS2):c.685A>G(p.Ile229Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,210,012 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

PRPS2
NM_002765.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Variant links:

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]

PRPS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.190274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPS2	NM_002765.5 linkuse as main transcript	c.685A>G	p.Ile229Val	missense_variant	5/7	ENST00000380668.10	NP_002756.1	P11908-1
PRPS2	NM_001039091.3 linkuse as main transcript	c.694A>G	p.Ile232Val	missense_variant	5/7		NP_001034180.1	P11908-2A0A140VK41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRPS2	ENST00000380668.10 linkuse as main transcript	c.685A>G	p.Ile229Val	missense_variant	5/7	1	NM_002765.5	ENSP00000370043.5	P11908-1
PRPS2	ENST00000398491.6 linkuse as main transcript	c.694A>G	p.Ile232Val	missense_variant	5/7	1		ENSP00000381504.2	P11908-2
PRPS2	ENST00000461630.1 linkuse as main transcript	c.270-983A>G		intron_variant		1		ENSP00000418911.1	H7C540

Frequencies

GnomAD3 genomes

AF:

0.0000710

AC:

AN:

112640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34778

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000934

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

181668

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66194

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1097372

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362756

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000832

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000710

AC:

AN:

112640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34778

show subpopulations

Gnomad4 AFR

AF:

0.000194

Gnomad4 AMR

AF:

0.0000934

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.694A>G (p.I232V) alteration is located in exon 5 (coding exon 5) of the PRPS2 gene. This alteration results from a A to G substitution at nucleotide position 694, causing the isoleucine (I) at amino acid position 232 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

T;.

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.16

Sift

Benign

0.060

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

0.0010

B;B

Vest4

0.20

MVP

0.66

MPC

1.2

ClinPred

0.081

GERP RS

4.9

Varity_R

0.35

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over