4-36091884-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015230.4(ARAP2):c.4422G>A(p.Val1474=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,599,982 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (6 hom.)
• Consequence: ARAP2 NM_015230.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.553

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-36091884-C-T is Benign according to our data. Variant chr4-36091884-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.553 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAP2	NM_015230.4	c.4422G>A	p.Val1474=	synonymous_variant	28/33	ENST00000303965.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAP2	ENST00000303965.9	c.4422G>A	p.Val1474=	synonymous_variant	28/33	1	NM_015230.4	P1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152150 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000550 AC: 137 AN: 248894 Hom.: 0 AF XY: 0.000639 AC XY: 86 AN XY: 134582

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.000602

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000463

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000532

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.000493 AC: 714 AN: 1447714 Hom.: 6 Cov.: 30 AF XY: 0.000512 AC XY: 368 AN XY: 718880

Gnomad4 AFR exome AF: 0.000813

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.000661

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000424

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152268 Hom.: 3 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74436

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000417 Hom.: 0

Bravo AF: 0.000865

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ARAP2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.0
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs145513915; hg19: chr4-36093506;