NM_003611.3(OFD1):c.2336G>A (p.Arg779Lys) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV002706296.2

Allele description

NM_003611.3(OFD1):c.2336G>A (p.Arg779Lys)

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.2336G>A (p.Arg779Lys)

HGVS:

NC_000023.11:g.13761160G>A
NG_008872.1:g.31448G>A
NG_008872.2:g.51657G>A
NG_146693.1:g.511G>A
NM_001330209.2:c.2216G>A
NM_001330210.2:c.1916G>A
NM_003611.2:c.2336G>A
NM_003611.3:c.2336G>AMANE SELECT
NP_001317138.1:p.Arg739Lys
NP_001317139.1:p.Arg639Lys
NP_003602.1:p.Arg779Lys
NC_000023.10:g.13779279G>A

Protein change:

R639K

Molecular consequence:

NM_001330209.2:c.2216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330210.2:c.1916G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003611.3:c.2336G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003001659	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 11, 2024)	germline	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

SCV003001659

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 11, 2024)

germline

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003001659.2

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

Description

This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 779 of the OFD1 protein (p.Arg779Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1960078). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt OFD1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine