ARAP2 p.Val1474Val

Variant names:

• chr4-36091883-T-T
• NM_015230.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-36091884--
• chr4-36091884-C-A
• chr4-36091884-C-G
• chr4-36091884-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015230.4(ARAP2):​c. variant causes a splice region, exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARAP2 NM_015230.4 splice_region, exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	NM_015230.4	MANE Select	c.		splice_region exon_region	Exon 28 of 33	NP_056045.2
	ARAP2	NR_146893.2		n.		splice_region exon_region	Exon 28 of 37
	ARAP2	NR_146894.2		n.		splice_region exon_region	Exon 28 of 33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP2	ENST00000303965.9	TSL:1 MANE Select	c.		splice_region exon_region	Exon 28 of 33	ENSP00000302895.4	Q8WZ64
	ARAP2	ENST00000942324.1		c.		splice_region exon_region	Exon 28 of 33	ENSP00000612383.1
	ARAP2	ENST00000905954.1		c.		splice_region exon_region	Exon 27 of 32	ENSP00000576013.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-36093505;