rs769890385
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_198525.3(KIF7):c.2737_2739del(p.Lys913del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000184 in 1,548,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. K913K) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
KIF7
NM_198525.3 inframe_deletion
NM_198525.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_198525.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.2737_2739del | p.Lys913del | inframe_deletion | 14/19 | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.2737_2739del | p.Lys913del | inframe_deletion | 14/19 | 5 | NM_198525.3 | P2 | |
KIF7 | ENST00000696512.1 | c.2860_2862del | p.Lys954del | inframe_deletion | 14/19 | A2 | |||
KIF7 | ENST00000677187.1 | n.411_413del | non_coding_transcript_exon_variant | 2/7 |
Frequencies
GnomAD3 genomes ? AF: 0.000137 AC: 20AN: 145722Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000159 AC: 39AN: 245778Hom.: 0 AF XY: 0.000165 AC XY: 22AN XY: 133234
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GnomAD4 exome AF: 0.000189 AC: 265AN: 1403080Hom.: 0 AF XY: 0.000183 AC XY: 128AN XY: 697666
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 22, 2017 | - - |
Acrocallosal syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This variant, c.2737_2739del, results in the deletion of 1 amino acid(s) of the KIF7 protein (p.Lys913del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs769890385, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with KIF7-related conditions. ClinVar contains an entry for this variant (Variation ID: 445340). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Intellectual disability Benign:1
Likely benign, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at