NM_003611.3(OFD1):c.111+2T>G AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 18, 2020
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:: RCV001380141.6

Allele description [Variation Report for NM_003611.3(OFD1):c.111+2T>G]

NM_003611.3(OFD1):c.111+2T>G

Genes:

LOC126863212:CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:13752241-13753440 [Gene]
OFD1:OFD1 centriole and centriolar satellite protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.2

Genomic location:

Preferred name:

NM_003611.3(OFD1):c.111+2T>G

HGVS:

NC_000023.11:g.13735348T>G
NG_008872.1:g.5636T>G
NG_008872.2:g.25845T>G
NG_011555.1:g.4276A>C
NG_087708.2:g.1327T>G
NM_001330209.2:c.111+2T>G
NM_001330210.2:c.-435+2T>G
NM_003611.3:c.111+2T>GMANE SELECT
NC_000023.10:g.13753467T>G

Links:

dbSNP: rs312262809

NCBI 1000 Genomes Browser:

rs312262809

Molecular consequence:

NM_001330209.2:c.111+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001330210.2:c.-435+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003611.3:c.111+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

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

Name:: Orofaciodigital syndrome I (OFD1)
Synonyms:: OFDS I; Orofaciodigital syndrome 1; OFD syndrome 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010702; MedGen: C1510460; Orphanet: 2750; OMIM: 311200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001578089	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 18, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 16783569, 27081566, 18546297, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001578089

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 18, 2020)

germline

clinical testing

PubMed (5)
[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

A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome.

Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH.

Hum Genet. 2006 Sep;120(2):171-8. Epub 2006 Jun 17.

PubMed [citation]

PMID:: 16783569

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001578089.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a donor splice site in intron 2 of the OFD1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OFD1 are known to be pathogenic (PMID: 16783569, 18546297, 27081566). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with Oral-facial-digital syndrome (PMID: 18546297). In at least one individual the variant was observed to be de novo.

#	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: Mar 5, 2024

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