11-47166315-C-G

Variant names:

• chr11-47166315-C-G
• NM_032389.6:c.1498G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032389.6(ARFGAP2):​c.1498G>C​(p.Ala500Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

ARFGAP2 (HGNC:13504): (ADP ribosylation factor GTPase activating protein 2) Predicted to enable GTPase activator activity. Predicted to be involved in COPI coating of Golgi vesicle. Located in Golgi apparatus; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGAP2	NM_032389.6	c.1498G>C	p.Ala500Pro	missense_variant	Exon 15 of 16	ENST00000524782.6	NP_115765.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGAP2	ENST00000524782.6	c.1498G>C	p.Ala500Pro	missense_variant	Exon 15 of 16	1	NM_032389.6	ENSP00000434442.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1498G>C (p.A500P) alteration is located in exon 15 (coding exon 15) of the ARFGAP2 gene. This alteration results from a G to C substitution at nucleotide position 1498, causing the alanine (A) at amino acid position 500 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.6	.;.;H
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.0	.;.;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.92
MutPred		0.66		.;.;Loss of MoRF binding (P = 0.0471);
MVP		0.65
MPC		0.96
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.96
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47187866;