NM_003611.3(OFD1):c.935+1G>C AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 12, 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:: RCV003809322.2

Allele description [Variation Report for NM_003611.3(OFD1):c.935+1G>C]

NM_003611.3(OFD1):c.935+1G>C

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.935+1G>C

HGVS:

NC_000023.11:g.13749534G>C
NG_008872.1:g.19822G>C
NG_008872.2:g.40031G>C
NM_001330209.2:c.935+1G>C
NM_001330210.2:c.515+1G>C
NM_003611.3:c.935+1G>CMANE SELECT
NC_000023.10:g.13767653G>C

Molecular consequence:

NM_001330209.2:c.935+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001330210.2:c.515+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003611.3:c.935+1G>C - 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
SCV004595346	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 12, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 16783569, 18546297, 27081566, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004595346

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 12, 2023)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004595346.1

#	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 9 of the OFD1 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 OFD1 are known to be pathogenic (PMID: 16783569, 18546297, 27081566). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of X-linked dominant oral-facial-digital syndrome (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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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