Description
Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated individuals (ClinVar ID: VCV000013329.17, PMID: 26817465, 19352411, 32164556, 31560489, 25533962, PS2 and PS4). The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.9, 3Cnet: 0.971, PP3). Patient's phenotype is considered compatible with Noonan syndrome 1 (3billion dataset, PP4).Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
# | Sample | Method | Observation |
---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
---|
1 | germline | yes | 1 | not provided | not provided | | 1 | not provided | not provided | not provided |