Genetic Variant ARFGAP2:p.Ser520Thr (chr11-47165490-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032389.6(ARFGAP2):c.1558T>A(p.Ser520Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000432 in 1,575,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ARFGAP2
NM_032389.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047585666).

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.1558T>A	p.Ser520Thr	missense	Exon 16 of 16	NP_115765.2
ARFGAP2	NM_001410995.1		c.1600T>A	p.Ser534Thr	missense	Exon 17 of 17	NP_001397924.1	E9PN48
ARFGAP2	NM_001242832.2		c.1474T>A	p.Ser492Thr	missense	Exon 15 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.1558T>A	p.Ser520Thr	missense	Exon 16 of 16	ENSP00000434442.1	Q8N6H7-1
ARFGAP2	ENST00000892878.1		c.1675T>A	p.Ser559Thr	missense	Exon 17 of 17	ENSP00000562937.1
ARFGAP2	ENST00000946556.1		c.1645T>A	p.Ser549Thr	missense	Exon 17 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000903

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.00

Gnomad OTH

AF:

0.000483

GnomAD2 exomes

AF:

0.0000801

AC:

AN:

212340

AF XY:

0.0000603

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.0000364

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1424148

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

708536

show subpopulations

African (AFR)

AF:

0.000681

AC:

AN:

30830

American (AMR)

AF:

0.0000254

AC:

AN:

39356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

37276

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093450

Other (OTH)

AF:

0.0000342

AC:

AN:

58464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000277

AC:

AN:

151508

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.000900

AC:

AN:

41100

American (AMR)

AF:

0.000263

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67908

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000565

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.014

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

PhyloP100

7.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

REVEL

Benign

0.25

Sift

Benign

0.082

Sift4G

Benign

0.12

Polyphen

0.39

Vest4

0.37

MVP

0.33

MPC

0.41

ClinPred

0.081

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.56

Mutation Taster

=65/35

polymorphism

(source)

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

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