rs1553264036
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014875.3(KIF14):c.246del(p.Asn83IlefsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
KIF14
NM_014875.3 frameshift
NM_014875.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.609
Genes affected
KIF14 (HGNC:19181): (kinesin family member 14) This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 1-200618477-TA-T is Pathogenic according to our data. Variant chr1-200618477-TA-T is described in ClinVar as [Pathogenic]. Clinvar id is 503570.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-200618477-TA-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF14 | NM_014875.3 | c.246del | p.Asn83IlefsTer3 | frameshift_variant | 2/30 | ENST00000367350.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF14 | ENST00000367350.5 | c.246del | p.Asn83IlefsTer3 | frameshift_variant | 2/30 | 2 | NM_014875.3 | P1 | |
KIF14 | ENST00000614960.4 | c.246del | p.Asn83IlefsTer3 | frameshift_variant | 1/29 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727220
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GnomAD4 genome ? Cov.: 33
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Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Microcephaly 20, primary, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 29, 2018 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at