Description
The sequence change, c.2852G>A, in exon 29 results in an amino acid change, p.Arg951Gln. This sequence change has been described in the gnomAD database with a low population frequency of 0.01% in European sub-population (dbSNP rs755922289). The p.Arg951Gln change affects a highly conserved amino acid residue located in a domain of the FANCA protein that is not known to be functional. The p.Arg951Gln substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). The p.Arg951Gln change has been reported in several individuals with Fanconi anemia (PMID: 17924555, 22778927, 24584348). In one of these individuals, this sequence change was shown to be in trans with a different pathogenic sequence change (PMID: 24584348). A different pathogenic sequence change affecting the same amino acid residue, p.Arg951Trp, has also been described in patients with FANCA-related disorders (PMID: 22778927, 17924555, 24584348, 26799702, 17924555, 24584348, 24349332). Functional studies have demonstrated disrupted protein function in the presence of the p.Arg951Gln change (PMID: 12697994). These collective evidences indicate that this sequence change is likely pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |