Submissions for variant NM_198525.3(KIF7):c.2944G>T (p.Glu982Ter)

gnomAD frequency: 0.00001  dbSNP: rs797045093

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000190601	SCV000245629	pathogenic	Acrocallosal syndrome	2014-11-25	criteria provided, single submitter	clinical testing	The p.Glu982X variant in KIF7 has not been previously reported in individuals with disease and data from large population studies is insufficient to assess the frequency of this variant. This nonsense variant leads to a premature termination codon at position 982 which is predicted to lead to a truncated or absent protein. Loss of function variants in KIF7 have been shown to cause Acrocallosal syndrome. In summary, this variant meets our criteria to be classified as pathogenic for Acrocallosal syndrome in an autosomal recessive manner.
UW Hindbrain Malformation Research Program, University of Washington	RCV000190601	SCV000256439	pathogenic	Acrocallosal syndrome	2015-02-23	criteria provided, single submitter	research
PreventionGenetics, part of Exact Sciences	RCV004742322	SCV005360119	pathogenic	KIF7-related disorder	2024-09-01	no assertion criteria provided	clinical testing	The KIF7 c.2944G>T variant is predicted to result in premature protein termination (p.Glu982*). This variant was reported in the compound heterozygous state in an individual with Joubert syndrome (Table S5, Bachmann-Gagescu et al. 2015. PubMed ID: 26092869). This variant is reported in 0.0024% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in KIF7 are expected to be pathogenic. This variant is interpreted as pathogenic.