Genetic Variant ARAP2:p.Gln1701His (chr4-36067919-C-A) – 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_015230.4(ARAP2):c.5103G>T(p.Gln1701His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00086 in 1,574,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 1 hom. )

Consequence

ARAP2
NM_015230.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.215

Publications

6 publications found

Variant links:

Genes affected

ARAP2 (HGNC:16924): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2) The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]

ARAP2 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=0.012206733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARAP2	NM_015230.4	MANE Select	c.5103G>T	p.Gln1701His	missense	Exon 33 of 33	NP_056045.2
ARAP2	NR_146894.2		n.5564G>T		non_coding_transcript_exon	Exon 33 of 33
ARAP2	NR_146893.2		n.5233+5770G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARAP2	ENST00000303965.9	TSL:1 MANE Select	c.5103G>T	p.Gln1701His	missense	Exon 33 of 33	ENSP00000302895.4	Q8WZ64
ARAP2	ENST00000503225.5	TSL:1	n.147+5770G>T		intron	N/A
ARAP2	ENST00000942324.1		c.5103G>T	p.Gln1701His	missense	Exon 33 of 33	ENSP00000612383.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000496

AC:

114

AN:

229992

AF XY:

0.000483

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000651

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000850

Gnomad OTH exome

AF:

0.000364

GnomAD4 exome

AF:

0.000898

AC:

1278

AN:

1422604

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

626

AN XY:

702606

show subpopulations

African (AFR)

AF:

0.000157

AC:

AN:

31804

American (AMR)

AF:

0.000806

AC:

AN:

38458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24540

East Asian (EAS)

AF:

0.00

AC:

AN:

39036

South Asian (SAS)

AF:

0.00

AC:

AN:

81140

European-Finnish (FIN)

AF:

0.0000568

AC:

AN:

52824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00111

AC:

1208

AN:

1090654

Other (OTH)

AF:

0.000529

AC:

AN:

58572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

150

200

250

<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:

0.000506

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41536

American (AMR)

AF:

0.000327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000868

AC:

AN:

68006

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000737

Hom.:

Bravo

AF:

0.000616

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000437

AC:

EpiCase

AF:

0.000882

EpiControl

AF:

0.000896

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

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.2

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.023

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.42

M_CAP

Benign

0.0047

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PhyloP100

0.21

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.044

Sift

Benign

0.053

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.057

MutPred

0.12

Gain of helix (P = 0.0496)

MVP

0.11

MPC

0.024

ClinPred

0.0050

GERP RS

-0.093

Varity_R

0.040

gMVP

0.48

Mutation Taster

=100/0

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