11-47166876-G-C

Variant names:

• chr11-47166876-G-C
• rs35950498
• NM_032389.6:c.1216C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032389.6(ARFGAP2):​c.1216C>G​(p.Arg406Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406W) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1744422).

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.1216C>G	p.Arg406Gly	missense	Exon 13 of 16	NP_115765.2
	ARFGAP2	NM_001410995.1		c.1258C>G	p.Arg420Gly	missense	Exon 14 of 17	NP_001397924.1	E9PN48
	ARFGAP2	NM_001242832.2		c.1132C>G	p.Arg378Gly	missense	Exon 12 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.1216C>G	p.Arg406Gly	missense	Exon 13 of 16	ENSP00000434442.1	Q8N6H7-1
	ARFGAP2	ENST00000892878.1		c.1333C>G	p.Arg445Gly	missense	Exon 14 of 17	ENSP00000562937.1
	ARFGAP2	ENST00000946556.1		c.1303C>G	p.Arg435Gly	missense	Exon 14 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 40 AN: 250754 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000337 AC: 493 AN: 1461268 Hom.: 0 Cov.: 34 AF XY: 0.000334 AC XY: 243 AN XY: 726966

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000134 AC: 6 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000410 AC: 456 AN: 1111920

Other (OTH) AF: 0.000497 AC: 30 AN: 60384

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74332

African (AFR) AF: 0.0000965 AC: 4 AN: 41434

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00000667 Hom.: 8

Bravo AF: 0.000223

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.9
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.38
MPC		0.96
ClinPred		0.69	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.59
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs35950498; hg19: chr11-47188427;