rs1064793001

Positions:

• chr19-7467500-GCGAGCGGCTGGAGCAGGAGCGGGC-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001367823.1(ARHGEF18):​c.3302_3325del​(p.Arg1101_Glu1108del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGEF18 NM_001367823.1 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.72

Genes affected

ARHGEF18 (HGNC:17090): (Rho/Rac guanine nucleotide exchange factor 18) Rho GTPases are GTP binding proteins that regulate a wide spectrum of cellular functions. These cellular processes include cytoskeletal rearrangements, gene transcription, cell growth and motility. Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GEF family. Family members share a common feature, a Dbl (DH) homology domain followed by a pleckstrin (PH) homology domain. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2018]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001367823.1.
• PP5: Variant 19-7467500-GCGAGCGGCTGGAGCAGGAGCGGGC-G is Pathogenic according to our data. Variant chr19-7467500-GCGAGCGGCTGGAGCAGGAGCGGGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 417756.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-7467500-GCGAGCGGCTGGAGCAGGAGCGGGC-G is described in Lovd as [Pathogenic]. Variant chr19-7467500-GCGAGCGGCTGGAGCAGGAGCGGGC-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF18	NM_001367823.1	c.3302_3325del	p.Arg1101_Glu1108del	inframe_deletion	26/29	ENST00000668164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF18	ENST00000668164.2	c.3302_3325del	p.Arg1101_Glu1108del	inframe_deletion	26/29		NM_001367823.1	A2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 78 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1064793001; hg19: chr19-7532386;