14-24238635-G-C

Position:

• chr14-24238635-G-C

Variant summary

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

The NM_001002002.3(GMPR2):​c.904G>C​(p.Glu302Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GMPR2 NM_001002002.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

Genes affected

GMPR2 (HGNC:4377): (guanosine monophosphate reductase 2) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP). The protein also functions in the re-utilization of free intracellular bases and purine nucleosides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

GMPR2 (HGNC:):

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=0.32406038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMPR2	NM_001002002.3	c.904G>C	p.Glu302Gln	missense_variant	10/10	ENST00000399440.7	NP_001002002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMPR2	ENST00000399440.7	c.904G>C	p.Glu302Gln	missense_variant	10/10	1	NM_001002002.3	ENSP00000382369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.958G>C (p.E320Q) alteration is located in exon 9 (coding exon 9) of the GMPR2 gene. This alteration results from a G to C substitution at nucleotide position 958, causing the glutamic acid (E) at amino acid position 320 to be replaced by a glutamine (Q). 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	0.10
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;T;T;T;.;T;.;.;.;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.8	.;L;L;.;.;L;.;.;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	.;N;N;N;.;N;N;N;N;N
REVEL	Uncertain	0.52
Sift	Benign	0.045	.;D;D;D;.;D;D;T;D;D
Sift4G	Benign	0.18	T;T;T;T;T;T;T;T;T;T
Polyphen		0.010, 0.068	.;B;B;.;.;B;B;.;.;.
Vest4		0.32
MVP		0.84
MPC		0.18
ClinPred		0.74	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.38
gMVP		0.41

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: rs2040467821; hg19: chr14-24707841;