NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 1, 2023
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:: RCV000146976.26

Allele description [Variation Report for NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs)]

NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs)

Gene:

OFD1:OFD1 centriole and centriolar satellite protein [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xp22.2

Genomic location:

Preferred name:

NM_003611.3(OFD1):c.1193_1196del (p.Gln398fs)

HGVS:

NC_000023.11:g.13755210AATC[1]
NG_008872.1:g.25498AATC[1]
NM_001330209.2:c.1073_1076del
NM_001330210.2:c.773_776del
NM_003611.3:c.1193_1196delMANE SELECT
NP_001317138.1:p.Gln358fs
NP_001317139.1:p.Gln258fs
NP_003602.1:p.Gln398fs
NC_000023.10:g.13773329AATC[1]
NM_003611.2:c.1193_1196delAATC

Protein change:

Q258fs

Links:

dbSNP: rs312262868

NCBI 1000 Genomes Browser:

rs312262868

Molecular consequence:

NM_001330209.2:c.1073_1076del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330210.2:c.773_776del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003611.3:c.1193_1196del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Fut1 fucosyltransferase 1 [Rattus norvegicus]
Fut1 fucosyltransferase 1 [Rattus norvegicus]
Gene ID:81919

Gene
81919[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000194312	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000329446	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 9, 2017)	germline	clinical testing	Citation Link,
SCV003917761	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000194312

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2007)

Pathogenic
(Feb 8, 2013)

germline

clinical testing

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

SCV000329446

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 9, 2017)

germline

clinical testing

Citation Link,

SCV003917761

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jan 1, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000194312.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV000329446.6

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

Description

The c.1193_1196delAATC pathogenic variant in the OFD1 gene has been reported previously in association with Oral-Facial-Digital syndrome type 1 (OFD1), including a de novo occurrence (Shimojima et al., 2013; Prattichizzo et al., 2008). The deletion causes a frameshift starting with codon Glutamine 398, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Gln398LeufsX2. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, the variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.

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

From CeGaT Center for Human Genetics Tuebingen, SCV003917761.13

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

Description

OFD1: PVS1, PS2, PM2

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

Last Updated: Nov 10, 2024

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