Genetic Variant ARFGAP2:p.Arg397Pro (chr11-47167924-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032389.6(ARFGAP2):c.1190G>C(p.Arg397Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,326 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. R397Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARFGAP2
NM_032389.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.59

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:

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ACMG classification

Classification was made for transcript

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=0.23235929).

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.1190G>C	p.Arg397Pro	missense	Exon 12 of 16	NP_115765.2
ARFGAP2	NM_001410995.1		c.1232G>C	p.Arg411Pro	missense	Exon 13 of 17	NP_001397924.1	E9PN48
ARFGAP2	NM_001242832.2		c.1106G>C	p.Arg369Pro	missense	Exon 11 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.1190G>C	p.Arg397Pro	missense	Exon 12 of 16	ENSP00000434442.1	Q8N6H7-1
ARFGAP2	ENST00000892878.1		c.1307G>C	p.Arg436Pro	missense	Exon 13 of 17	ENSP00000562937.1
ARFGAP2	ENST00000946556.1		c.1277G>C	p.Arg426Pro	missense	Exon 13 of 17	ENSP00000616615.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246174

AF XY:

0.00000751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459326

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110812

Other (OTH)

AF:

0.00

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0095

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

PhyloP100

3.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Benign

0.25

Polyphen

0.90

Vest4

0.47

MutPred

0.25

Loss of MoRF binding (P = 0.0037)

MVP

0.19

MPC

0.98

ClinPred

0.71

GERP RS

6.0

Varity_R

0.34

gMVP

0.20

Mutation Taster

=22/78

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over