NM_001173990.3(TMEM216):c.253C>T (p.Arg85Ter) AND Joubert syndrome 2

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 21, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000201650.14

Allele description [Variation Report for NM_001173990.3(TMEM216):c.253C>T (p.Arg85Ter)]

NM_001173990.3(TMEM216):c.253C>T (p.Arg85Ter)

Gene:

TMEM216:transmembrane protein 216 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.2

Genomic location:

Preferred name:

NM_001173990.3(TMEM216):c.253C>T (p.Arg85Ter)

Other names:

p.Arg85*

HGVS:

NC_000011.10:g.61397797C>T
NG_032976.1:g.10438C>T
NM_001173990.3:c.253C>TMANE SELECT
NM_001173991.3:c.253C>T
NM_001330285.2:c.70C>T
NM_016499.6:c.70C>T
NP_001167461.1:p.Arg85Ter
NP_001167462.1:p.Arg85Ter
NP_001317214.1:p.Arg24Ter
NP_057583.2:p.Arg24Ter
LRG_698t1:c.253C>T
LRG_698t2:c.253C>T
LRG_698:g.10438C>T
LRG_698p1:p.Arg85Ter
LRG_698p2:p.Arg85Ter
NC_000011.9:g.61165269C>T
NM_001173990.2:c.253C>T
NM_001173991.1:c.253C>T
NM_001173991.2:c.253C>T

Protein change:

R24*

Links:

dbSNP: rs11230683

NCBI 1000 Genomes Browser:

rs11230683

Molecular consequence:

NM_001173990.3:c.253C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001173991.3:c.253C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001330285.2:c.70C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_016499.6:c.70C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Joubert syndrome 2 (JBTS2)
Synonyms:: Cerebellooculorenal syndrome 2
Identifiers:: MONDO: MONDO:0011963; MedGen: C1842577; Orphanet: 2318; OMIM: 608091

Recent activity

Clear Turn Off Turn On

Mus musculus ST3 beta-galactoside alpha-2,3-sialyltransferase 3 (St3gal3), trans...
Mus musculus ST3 beta-galactoside alpha-2,3-sialyltransferase 3 (St3gal3), transcript variant 1, mRNA
gi|2725763532|ref|NM_009176.6|

Nucleotide
LOC109851546 [Asparagus officinalis]
LOC109851546 [Asparagus officinalis]
Gene ID:109851546

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000256484	UW Hindbrain Malformation Research Program, University of Washington See additional submitters University of Washington Center for Mendelian Genomics, University of Washington	criteria provided, single submitter (Bachmann-Gagescu et al. (J Med Genet. 2015))	Pathogenic (Feb 23, 2015)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000920296	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 5, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28497568, 23351400, 20512146 Citation Link,
SCV004206190	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 21, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000256484

UW Hindbrain Malformation Research Program, University of Washington

See additional submitters

criteria provided, single submitter

(Bachmann-Gagescu et al. (J Med Genet. 2015))

Pathogenic
(Feb 23, 2015)

unknown

research

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

SCV000920296

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 5, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV004206190

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 21, 2024)

unknown

clinical testing

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

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.

Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, Rue TC, Ishak GE, Isabella CR, Gorden N, Adkins J, Boyle EA, de Lacy N, O'Day D, Alswaid A, Ramadevi A R, Lingappa L, Lourenço C, Martorell L, Garcia-Cazorla À, Ozyürek H, Haliloğlu G, Tuysuz B, et al.

J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.

PubMed [citation]

PMID:: 26092869
PMCID:: PMC5082428

Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

Summers AC, Snow J, Wiggs E, Liu AG, Toro C, Poretti A, Zein WM, Brooks BP, Parisi MA, Inati S, Doherty D, Vemulapalli M, Mullikin JC; NISC Comparative Sequencing Program., Vilboux T, Gahl WA, Gunay-Aygun M.

Am J Med Genet A. 2017 Jul;173(7):1796-1812. doi: 10.1002/ajmg.a.38272. Epub 2017 May 12.

PubMed [citation]

PMID:: 28497568
PMCID:: PMC5682233

See all PubMed Citations (5)

Details of each submission

From UW Hindbrain Malformation Research Program, University of Washington, SCV000256484.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920296.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: TMEM216 c.253C>T (p.Arg85X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.7e-05 in 276782 control chromosomes. This frequency is not higher than expected for a pathogenic variant in TMEM216 causing Joubert Syndrome 2 (8.7e-05 vs 0.0039), allowing no conclusion about variant significance. c.253C>T has been reported in the literature in individuals affected with Meckel syndrome 2 or Joubert Syndrome 2 (Valente 2010, Summers 2017). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, demonstrating the loss of protein expression and a failure in ciliogenesis and centrosome docking (Valente 2010). The most pronounced variant effect results in <10% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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

From Baylor Genetics, SCV004206190.2

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

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

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine