NM_001174150.2(ARL13B):c.599G>A (p.Arg200His) AND Joubert syndrome 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001859504.4

Allele description [Variation Report for NM_001174150.2(ARL13B):c.599G>A (p.Arg200His)]

NM_001174150.2(ARL13B):c.599G>A (p.Arg200His)

Gene:

ARL13B:ADP ribosylation factor like GTPase 13B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q11.2

Genomic location:

Preferred name:

NM_001174150.2(ARL13B):c.599G>A (p.Arg200His)

HGVS:

NC_000003.12:g.94036664G>A
NG_017076.1:g.61526G>A
NM_001174150.2:c.599G>AMANE SELECT
NM_001174151.2:c.290G>A
NM_001321328.2:c.554G>A
NM_144996.4:c.278G>A
NM_182896.2:c.599G>A
NM_182896.3:c.599G>A
NP_001167621.1:p.Arg200His
NP_001167622.1:p.Arg97His
NP_001308257.1:p.Arg185His
NP_659433.2:p.Arg93His
NP_878899.1:p.Arg200His
NC_000003.11:g.93755508G>A
NM_001174150.1:c.599G>A
NR_033427.2:n.623G>A
NR_135621.2:n.614G>A
p.(Arg200His)

Protein change:

R185H

Links:

dbSNP: rs764109067

NCBI 1000 Genomes Browser:

rs764109067

Molecular consequence:

NM_001174150.2:c.599G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174151.2:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321328.2:c.554G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_144996.4:c.278G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_182896.3:c.599G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033427.2:n.623G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135621.2:n.614G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Joubert syndrome 8 (JBTS8)
Identifiers:: MONDO: MONDO:0012855; MedGen: C2676771; Orphanet: 475; OMIM: 612291

Recent activity

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homologue of retroviral POL genes [Cladosporium fulvum T-1 virus]
homologue of retroviral POL genes [Cladosporium fulvum T-1 virus]
Gene ID:40526545

Gene
dop-2 Dopamine receptor 2 [Caenorhabditis elegans]
dop-2 Dopamine receptor 2 [Caenorhabditis elegans]
Gene ID:179347

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236173	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18674751, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236173

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 31, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome.

Cantagrel V, Silhavy JL, Bielas SL, Swistun D, Marsh SE, Bertrand JY, Audollent S, Attié-Bitach T, Holden KR, Dobyns WB, Traver D, Al-Gazali L, Ali BR, Lindner TH, Caspary T, Otto EA, Hildebrandt F, Glass IA, Logan CV, Johnson CA, Bennett C, Brancati F; et al.

Am J Hum Genet. 2008 Aug;83(2):170-9. doi: 10.1016/j.ajhg.2008.06.023.

PubMed [citation]

PMID:: 18674751
PMCID:: PMC2495072

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002236173.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg200 amino acid residue in ARL13B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18674751). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARL13B protein function. ClinVar contains an entry for this variant (Variation ID: 266096). This missense change has been observed in individual(s) with Joubert syndrome and related disorders (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 200 of the ARL13B protein (p.Arg200His).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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