Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4PP5

The NM_001367823.1(ARHGEF18):c.3302_3325delGGCTGGAGCAGGAGCGGGCCGAGC(p.Arg1101_Glu1108del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R1101R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

ARHGEF18
NM_001367823.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.72

Publications

0 publications found

Variant links:

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]

ARHGEF18 Gene-Disease associations (from GenCC):

retinitis pigmentosa 78
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARHGEF18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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 VariationId is 417756.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367823.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARHGEF18	NM_001367823.1	MANE Select	c.3302_3325delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg1101_Glu1108del	disruptive_inframe_deletion	Exon 26 of 29	NP_001354752.1
ARHGEF18	NM_001130955.2		c.2576_2599delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg859_Glu866del	disruptive_inframe_deletion	Exon 16 of 20	NP_001124427.2
ARHGEF18	NM_001367824.1		c.2264_2287delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg755_Glu762del	disruptive_inframe_deletion	Exon 17 of 20	NP_001354753.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARHGEF18	ENST00000668164.2	MANE Select	c.3302_3325delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg1101_Glu1108del	disruptive_inframe_deletion	Exon 26 of 29	ENSP00000499655.2
ARHGEF18	ENST00000617428.4	TSL:1	c.2264_2287delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg755_Glu762del	disruptive_inframe_deletion	Exon 17 of 20	ENSP00000482647.4
ARHGEF18	ENST00000319670.14	TSL:1	c.2261_2284delGGCTGGAGCAGGAGCGGGCCGAGC	p.Arg754_Glu761del	disruptive_inframe_deletion	Exon 17 of 20	ENSP00000319200.8

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa 78 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.7

Mutation Taster

=100/100

disease causing (ClinVar)

(source)

Splicing

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

Publications

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rs1064793001

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over