ClinVar Miner

Submissions for variant NM_198525.3(KIF7):c.2896_2897del (p.Ala966fs)

gnomAD frequency: 0.00006  dbSNP: rs752248403
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000023881 SCV000636827 pathogenic Acrocallosal syndrome 2017-05-16 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides in exon 15 of the KIF7 mRNA (c.2896_2897delGC), causing a frameshift at codon 966. This creates a premature translational stop signal (p.Ala966Profs*81) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIF7 are known to be pathogenic. This particular variant has been reported to be homozygous in individuals affected with fetal hydrolethalus and acrocallosal syndromes (PMID: 215522264), as well as an individual with facial dysmorphism, intellectual disability, and dysgenesis of corpus callosum (PMID: 27081521). For these reasons, this variant has been classified as Pathogenic.
DASA RCV001849281 SCV002107078 pathogenic Multiple epiphyseal dysplasia, Al-Gazali type 2022-03-05 criteria provided, single submitter clinical testing The c.2896_2897delGC;p.(Ala966Profs*81) is a null frameshift variant (NMD) in the KIF7 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 30895; PMID: 21552264) - PS4. The variant is present at low allele frequencies population databases (rs752248403 – gnomAD 0.00006457%; ABraOM 0.000854 frequency - http://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
GeneDx RCV003327364 SCV004034347 pathogenic not provided 2023-09-09 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21552264, 27081521, 27894351, 31589614, 34884862)
Fulgent Genetics, Fulgent Genetics RCV005007892 SCV005642890 pathogenic Acrocallosal syndrome; Multiple epiphyseal dysplasia, Al-Gazali type; Hydrolethalus syndrome 2 2024-06-24 criteria provided, single submitter clinical testing
OMIM RCV000023880 SCV000045171 pathogenic Hydrolethalus syndrome 2 2011-06-01 no assertion criteria provided literature only
OMIM RCV000023881 SCV000045172 pathogenic Acrocallosal syndrome 2011-06-01 no assertion criteria provided literature only

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