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Here, we investigated the genetic cause of a complex neurodevelopmental phenotype in two Palestinian siblings. Whole exome sequencing identified a homozygous missense <jats:italic>TECPR2<\/jats:italic> variant (Chr14(GRCh38):g.102425085G&gt;A; NM_014844.5:c.745G&gt;A, p.(Gly249Arg)) absent in gnomAD, segregating appropriately with the inheritance pattern in the family. Variant assessment with <jats:italic>in silico<\/jats:italic> pathogenicity prediction and protein modeling tools alongside population database frequencies led to classification as a variant of uncertain significance. As pathogenic <jats:italic>TECPR2<\/jats:italic> variants are associated with hereditary sensory and autonomic neuropathy with intellectual disability, we reviewed previously published candidate <jats:italic>TECPR2<\/jats:italic> missense variants to clarify clinical outcomes and variant classification using current approved guidelines, classifying a number of published variants as of uncertain significance. This work highlights genomic healthcare inequalities and the challenges in interpreting rare genetic variants in populations underrepresented in genomic databases. It also improves understanding of the clinical and genetic spectrum of <jats:italic>TECPR2<\/jats:italic>\u2010related neuropathy and contributes to addressing genomic data disparity and inequalities of the genomic architecture in Palestinian populations.<\/jats:p>","DOI":"10.1002\/ajmg.a.63579","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T11:58:40Z","timestamp":1709553520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp><i>TECPR2<\/i><\/scp>\u2010related hereditary sensory and autonomic neuropathy in two siblings from Palestine"],"prefix":"10.1002","volume":"194","author":[{"given":"Reham","family":"Khalaf\u2010Nazzal","sequence":"first","affiliation":[{"name":"Faculty of Medicine Arab American University of Palestine  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Dweikat","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Arab American University of Palestine  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishanka","family":"Ubeyratna","sequence":"additional","affiliation":[{"name":"RILD Wellcome Wolfson Medical Research Centre Royal Devon University Hospitals NHS Foundation Trust, University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-9202","authenticated-orcid":false,"given":"James","family":"Fasham","sequence":"additional","affiliation":[{"name":"RILD Wellcome Wolfson Medical Research Centre Royal Devon University Hospitals NHS Foundation Trust, University of Exeter Medical School  Exeter UK"},{"name":"Peninsula Clinical Genetics Service Royal Devon &amp; 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