ARFGAP2 p.Gly474Arg

Variant names:

• chr11-47166512-C-G
• NM_032389.6:c.1420G>C
• ARFGAP2 p.Gly474Arg

Your query was ambiguous. Multiple possible variants found:

• chr11-47166512-C-G
• chr11-47166512-C-T
• chr11-47166510-TCC-ACG
• chr11-47166510-TCC-GCG
• chr11-47166510-TCC-CCG
• chr11-47166510-TCC-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032389.6(ARFGAP2):​c.1420G>C​(p.Gly474Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19583005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032389.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGAP2	NM_032389.6	MANE Select	c.1420G>C	p.Gly474Arg	missense	Exon 14 of 16	NP_115765.2
	ARFGAP2	NM_001410995.1		c.1462G>C	p.Gly488Arg	missense	Exon 15 of 17	NP_001397924.1	E9PN48
	ARFGAP2	NM_001242832.2		c.1336G>C	p.Gly446Arg	missense	Exon 13 of 15	NP_001229761.1	G5E9L0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGAP2	ENST00000524782.6	TSL:1 MANE Select	c.1420G>C	p.Gly474Arg	missense	Exon 14 of 16	ENSP00000434442.1	Q8N6H7-1
	ARFGAP2	ENST00000892878.1		c.1537G>C	p.Gly513Arg	missense	Exon 15 of 17	ENSP00000562937.1
	ARFGAP2	ENST00000946556.1		c.1507G>C	p.Gly503Arg	missense	Exon 15 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.83	L
PhyloP100		2.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.069
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Varity_R		0.059
gMVP		0.29
Mutation Taster		=76/24	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-47188063;