dbSNP rs35950498: ARFGAP2:p.Arg406Trp (chr11-47166876-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_032389.6(ARFGAP2):c.1216C>T(p.Arg406Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,546 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0055 ( 12 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 9 hom. )

Consequence

ARFGAP2
NM_032389.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.94

Publications

6 publications found

Variant links:

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]

ARFGAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065661967).

BP6

Variant 11-47166876-G-A is Benign according to our data. Variant chr11-47166876-G-A is described in ClinVar as Benign. ClinVar VariationId is 3045169.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0055 (838/152282) while in subpopulation AFR AF = 0.0176 (733/41550). AF 95% confidence interval is 0.0166. There are 12 homozygotes in GnomAd4. There are 394 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARFGAP2	NM_032389.6	MANE Select	c.1216C>T	p.Arg406Trp	missense	Exon 13 of 16	NP_115765.2
ARFGAP2	NM_001410995.1		c.1258C>T	p.Arg420Trp	missense	Exon 14 of 17	NP_001397924.1	E9PN48
ARFGAP2	NM_001242832.2		c.1132C>T	p.Arg378Trp	missense	Exon 12 of 15	NP_001229761.1	G5E9L0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARFGAP2	ENST00000524782.6	TSL:1 MANE Select	c.1216C>T	p.Arg406Trp	missense	Exon 13 of 16	ENSP00000434442.1	Q8N6H7-1
ARFGAP2	ENST00000892878.1		c.1333C>T	p.Arg445Trp	missense	Exon 14 of 17	ENSP00000562937.1
ARFGAP2	ENST00000946556.1		c.1303C>T	p.Arg435Trp	missense	Exon 14 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

839

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00227

AC:

568

AN:

250754

AF XY:

0.00182

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00856

Gnomad EAS exome

AF:

0.00441

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000977

AC:

1428

AN:

1461264

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

625

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.0184

AC:

615

AN:

33474

American (AMR)

AF:

0.00161

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00796

AC:

208

AN:

26118

East Asian (EAS)

AF:

0.00219

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000248

AC:

276

AN:

1111918

Other (OTH)

AF:

0.00253

AC:

153

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00550

AC:

838

AN:

152282

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0176

AC:

733

AN:

41550

American (AMR)

AF:

0.00196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.00289

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00693

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0189

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00262

AC:

318

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARFGAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.1

PhyloP100

1.9

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.66

MVP

0.30

MPC

0.86

ClinPred

0.066

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.60

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over