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NM_001173990.2(TMEM216):c.218G>T (p.Arg73Leu) AND Joubert syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 21, 2016
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:
RCV000465185.1

Allele description

NM_001173990.2(TMEM216):c.218G>T (p.Arg73Leu)

Gene:
TMEM216:transmembrane protein 216 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q12.2
Genomic location:
Preferred name:
NM_001173990.2(TMEM216):c.218G>T (p.Arg73Leu)
HGVS:
  • NC_000011.10:g.61393965G>T
  • NG_032976.1:g.6606G>T
  • NM_001173990.2:c.218G>T
  • NM_001173991.2:c.218G>T
  • NM_016499.5:c.35G>T
  • NP_001167461.1:p.Arg73Leu
  • NP_001167462.1:p.Arg73Leu
  • NP_057583.2:p.Arg12Leu
  • NC_000011.9:g.61161437G>T
  • Q9P0N5:p.Arg73Leu
Nucleotide change:
c.218G>T
Protein change:
R12L; ARG73LEU
Links:
UniProtKB: Q9P0N5#VAR_063388; OMIM: 613277.0001; dbSNP: rs201108965
NCBI 1000 Genomes Browser:
rs201108965
Allele Frequency:
0.00013(T)
Molecular consequence:
  • NM_001173990.2:c.218G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Joubert syndrome (JBTS)
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Familial aplasia of the vermis; Joubert Syndrome and Related Disorders; See all synonyms [MedGen]
Identifiers:
MedGen: C0431399; Orphanet: 475; OMIM: PS213300; Human Phenotype Ontology: HP:0002335

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000554071Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 21, 2016) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, SCV000554071.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with leucine at codon 73 of the TMEM216 protein (p.Arg73Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs201108965, ExAC 0.02%). This variant has been reported in many individuals and families affected with Meckel and Joubert syndrome-related disorders, most of whom are homozygous for this variant (PMID: 20512146, 20036350, 26092869). It has been described as an Ashkenazi Jewish founder variant, and is the most common disease-related variant reported in TMEM216 (PMID: 20512146, 20036350, 26092869). ClinVar contains an entry for this variant (Variation ID: 197). Experimental studies have shown that this missense change results in a 50% reduction in TMEM216 protein level, and that fibroblasts from affected individuals have decreased ciliogenesis (PMID: 20512146, 22282472). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 21, 2018