NM_001173990.3(TMEM216):c.35-13_36del AND Familial aplasia of the vermis

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 11, 2023
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:: RCV001851024.4

Allele description [Variation Report for NM_001173990.3(TMEM216):c.35-13_36del]

NM_001173990.3(TMEM216):c.35-13_36del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11q12.2

Genomic location:

Preferred name:

NM_001173990.3(TMEM216):c.35-13_36del

HGVS:

NC_000011.10:g.61393218_61393232del
NG_032976.1:g.5859_5873del
NM_001173990.3:c.35-13_36delMANE SELECT
NM_001173991.3:c.35-13_36del
NM_001330285.2:c.-149-13_-148del
NM_016499.6:c.-149-13_-148del
LRG_698t1:c.35-13_36del
LRG_698t2:c.35-13_36del
LRG_698:g.5859_5873del
NC_000011.9:g.61160688_61160702del
NC_000011.9:g.61160690_61160704del

Links:

dbSNP: rs1057520085

NCBI 1000 Genomes Browser:

rs1057520085

Molecular consequence:

NM_001173990.3:c.35-13_36del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001173991.3:c.35-13_36del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330285.2:c.-149-13_-148del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_016499.6:c.-149-13_-148del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Familial aplasia of the vermis
Synonyms:: CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002312171	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 20512146, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002312171

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 11, 2023)

germline

clinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes.

Valente EM, Logan CV, Mougou-Zerelli S, Lee JH, Silhavy JL, Brancati F, Iannicelli M, Travaglini L, Romani S, Illi B, Adams M, Szymanska K, Mazzotta A, Lee JE, Tolentino JC, Swistun D, Salpietro CD, Fede C, Gabriel S, Russ C, Cibulskis K, Sougnez C, et al.

Nat Genet. 2010 Jul;42(7):619-25. doi: 10.1038/ng.594. Epub 2010 May 30.

PubMed [citation]

PMID:: 20512146
PMCID:: PMC2894012

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002312171.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 376902). This variant has not been reported in the literature in individuals affected with TMEM216-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant results in the deletion of part of exon 2 (c.35-13_36del) of the TMEM216 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMEM216 are known to be pathogenic (PMID: 20512146).

#	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: Sep 29, 2024

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