rs1131690773
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006612.6(KIF1C):c.2478delA(p.Ala828ArgfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,439,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
KIF1C
NM_006612.6 frameshift
NM_006612.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -6.51
Publications
2 publications found
Genes affected
KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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;
PP5
Variant 17-5022558-GA-G is Pathogenic according to our data. Variant chr17-5022558-GA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 265862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.94e-7 AC: 1AN: 1439916Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1AN XY: 714240 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1439916
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
714240
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33110
American (AMR)
AF:
AC:
0
AN:
40910
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25646
East Asian (EAS)
AF:
AC:
0
AN:
38758
South Asian (SAS)
AF:
AC:
0
AN:
83382
European-Finnish (FIN)
AF:
AC:
0
AN:
51802
Middle Eastern (MID)
AF:
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1101044
Other (OTH)
AF:
AC:
1
AN:
59514
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spastic ataxia 2 Pathogenic:2
Aug 25, 2016
Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul University
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:case-control
- -
-
Genomics England Pilot Project, Genomics England
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Pathogenic:1
Oct 23, 2020
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational 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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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