ClinVar Miner

Submissions for variant NM_001189.4(NKX3-2):c.507_508del (p.Gly171fs)

dbSNP: rs1560165127
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Hacettepe Genetic Diseases Diagnosis Center, Hacettepe University Faculty of Medicine RCV000684827 SCV000732903 likely pathogenic Spondylo-megaepiphyseal-metaphyseal dysplasia 2018-03-30 no assertion criteria provided clinical testing The c.507_508delCA (p.Gly171Cysfs*55) in exon 2 (GRCh37, NM_001189.3) of NKX3-2 has not been reported previously in the literature. Index patient was an affected newborn with dysmorphic facial features and severe short trunk. The patient required immediate intubation at the delivery room and duodenal atresia was detected during his course in neonatal intensive care unit. Skeletal survey revealed total absence of ossification of the vertebral bodies, pubes, and ischia. The long bones were short and broad with flared metaphyses. The downward sloping or tented appearance of the ribs were distinctive. A diagnosis of “Spondylo-Megaepiphyseal-Metaphyseal Dysplasia” (SMMD) was made on clinical and radiological grounds. The patient was operated on postnatal day 7 for duodenal atresia. In the post-operative period he developed sepsis and respiratory failure and he died on postnatal day 14. Molecular analysis revealed homozygosity for a novel mutation, c.507_508delCA (p.Gly171Cysfs*55) in exon 2 of NKX3-2. Sanger sequencing revealed that father and mother were both heterozygous carriers for homozygous G171Cfs*55 variant in NKX3-2. This genetic change was predicted as "Disease Causing" by MutationTaster (with the score of 1.0). This genetic change was not present in our in-house database established within “Hacettepe Exome Project” which comprises 380 clinically unrelated Turkish individuals. In summary, the p.Gly171Cysfs*55 variant meets our criteria to be classified as “Likely pathogenic”.
OMIM RCV000684827 SCV000898487 pathogenic Spondylo-megaepiphyseal-metaphyseal dysplasia 2019-04-22 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.