Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000732836 | SCV000860828 | uncertain significance | not provided | 2018-05-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001088881 | SCV001098385 | likely benign | Acrocallosal syndrome | 2025-01-29 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000732836 | SCV001250424 | uncertain significance | not provided | 2019-09-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000732836 | SCV001776475 | likely benign | not provided | 2020-12-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005240516 | SCV005884403 | likely benign | not specified | 2024-12-26 | criteria provided, single submitter | clinical testing | Variant summary: KIF7 c.2549G>T (p.Arg850Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 1602052 control chromosomes, predominantly at a frequency of 0.004 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in KIF7 causing Acrocallosal Syndrome/Joubert Syndrome 12 phenotype. The variant, c.2549G>T, has been reported in the literature in a presumed compound heterozygous individual affected with thoracic insufficiency syndrome (Strong_2023); however, the phase of the two reported KIF7 variants was not specified in this study, and variant co-occurrence analysis in gnomAD v2.1 indicates that the two variants are on the same haplotype in most individuals. These report(s) do 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. The following publication has been ascertained in the context of this evaluation (PMID: 36653407). ClinVar contains an entry for this variant (Variation ID: 596872). Based on the evidence outlined above, the variant was classified as likely benign. |