rs312262845
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_003611.3(OFD1):c.709_710delAA(p.Lys237ValfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
OFD1
NM_003611.3 frameshift
NM_003611.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.04
Publications
11 publications found
Genes affected
OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]
OFD1 Gene-Disease associations (from GenCC):
- ciliopathyInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- Joubert syndrome 10Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- orofaciodigital syndrome IInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- retinitis pigmentosa 23Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- orofaciodigital syndrome type 6Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Simpson-Golabi-Behmel syndrome type 2Inheritance: XL Classification: LIMITED Submitted by: G2P
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1071989Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 346305
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1071989
Hom.:
AF XY:
AC XY:
0
AN XY:
346305
African (AFR)
AF:
AC:
0
AN:
25404
American (AMR)
AF:
AC:
0
AN:
33459
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18813
East Asian (EAS)
AF:
AC:
0
AN:
29651
South Asian (SAS)
AF:
AC:
0
AN:
51014
European-Finnish (FIN)
AF:
AC:
0
AN:
40110
Middle Eastern (MID)
AF:
AC:
0
AN:
4035
European-Non Finnish (NFE)
AF:
AC:
0
AN:
824524
Other (OTH)
AF:
AC:
0
AN:
44979
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -46
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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