ClinVar Miner

Submissions for variant NM_198525.3(KIF7):c.1220C>A (p.Ala407Asp)

gnomAD frequency: 0.00286  dbSNP: rs587780375
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000117411 SCV000151609 uncertain significance not provided 2013-09-16 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000117411 SCV000331870 uncertain significance not provided 2017-03-09 criteria provided, single submitter clinical testing
Invitae RCV001083297 SCV000636817 likely benign Acrocallosal syndrome 2021-12-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199843 SCV001370567 likely benign not specified 2020-05-08 criteria provided, single submitter clinical testing Variant summary: KIF7 c.1220C>A (p.Ala407Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0027 in 137568 control chromosomes, predominantly at a frequency of 0.0084 within the African or African-American subpopulation in the gnomAD database (v3 genomes dataset), including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 20 fold of the estimated maximal expected allele frequency for a pathogenic variant in KIF7 causing Acrocallosal Syndrome/Joubert Syndrome 12 phenotype (0.0004), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1220C>A has been reported in the literature in one individual affected with cerebellar ataxia (Sun_2019). This report did not provide unequivocal conclusions about association of the variant with Acrocallosal Syndrome/Joubert Syndrome 12. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000117411 SCV001754078 likely benign not provided 2021-06-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29915382)

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