ClinGen Dosage Sensitivity Curation Page

SPRED1

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
17704776 Brems et al (2007) reported loss-of-function autosomal dominant mutations in SPRED1 associated with a neurofibromatosis 1-like phenotype, including several nonsense, two frameshift, and a splice donor site mutation.
19443465 Spurlock et al (2009) screened 85 patients with a mild NF1-like phenotype (Legius syndrome) for SPRED1 mutations. SPRED1 mutations were identified in 6 cases; 5 were novel and included 3 nonsense (R16X, E73X, R262X), 2 frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp), and a single missense mutation (V44D). Short direct or inverted repeats detected immediately adjacent to some SPRED1 mutations may have led to the formation of the microdeletions and base pair substitutions

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.