ClinVar

Description

The p.Gln147Arg variant was identified in the literature in at least 2 of 96 proband chromosomes in individuals with Esophageal squamous cell cancer or cervical cancer (Zhong 2011, Kwong 2008). However, a second variant (c.7806-9T>G) was demonstrated to cause aberrant splicing and considered pathogenic was identified in the individual with cervical cancer and shown to segregate together with the p.Gln147Arg variant in at least 2 other affected family members and not in one unaffected family member, increasing the likelihood that the p.Gln147Arg variant does not have clinical significance. This residue is not conserved in mammals and the variant amino acid Arginine (Arg) is present in rat, mouse, dog, cat, opossum and chicken. Computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, increasing the likelihood this variant does not have clinical significance. The variant was identified in individuals of Asian background and our laboratory has tested a limited number of individuals from this population group such that this variant may prove to be a common or rare polymorphism in this population of origin. Furthermore, Myriad calls this variant a polymorphism (personal communication). Based on the above information this variant is considered benign.