ClinVar

Description

Variant summary: CFTR c.2908G>A (p.Gly970Ser) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. This variant also falls within exonic splice region in exon 26. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes the canonical 5' splicing donor site. One predict the variant weakens the canonical 5' donor site. One predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251120 control chromosomes. c.2908G>A has been reported in the literature in at-least three individuals affected with Cystic Fibrosis, without detailed information for analysis (Ortiz_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29178639). ClinVar contains an entry for this variant (Variation ID: 53589). Based on the evidence outlined above, the variant was classified as likely pathogenic.