17-18928832-G-A

Variant names:

• chr17-18928832-G-A
• NM_002767.4:c.826G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002767.4(PRPSAP2):​c.826G>A​(p.Asp276Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPSAP2 NM_002767.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3785336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPSAP2	NM_002767.4	c.826G>A	p.Asp276Asn	missense_variant	Exon 11 of 12	ENST00000268835.7	NP_002758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000268835.7	c.826G>A	p.Asp276Asn	missense_variant	Exon 11 of 12	1	NM_002767.4	ENSP00000268835.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.826G>A (p.D276N) alteration is located in exon 11 (coding exon 9) of the PRPSAP2 gene. This alteration results from a G to A substitution at nucleotide position 826, causing the aspartic acid (D) at amino acid position 276 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;.;.;T
Eigen	Benign	0.012
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.050	.;.;.;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.4	.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.14	.;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.015	.;.;.;B
Vest4		0.48
MutPred		0.58		.;.;.;Loss of loop (P = 0.0804);
MVP		0.76
MPC		0.91
ClinPred		0.73	D
GERP RS		5.2
Varity_R		0.21
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18832145;