Description
This variant has been reported in over 100 affected individuals as a homozygous or compound heterozygous change in patients with pontocerebellar hypoplasia and has been identified in 90% of individuals with pontocerebellar hypoplasia type 2 (PCH2, PMID: 24886362, 20301773). This variant has been shown to segregate with disease in more than 20 affected relatives from 10 families (PMID: 23307886, 21368912, 29410950, 20803644, 20956791, 23177318, 21468723, 21609947, 26701950, 27570394, 18711368, 24886362). Additionally, the c.919G>T (p.Ala307Ser) variant is a common homozygous missense variant that has been identified in 33 individuals, from nonconsanguineous families, who all survived until 11 years of age (PMID: 24886362). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.089% (213/240704) and thus is presumed to be rare. In silico analyses support a deleterious effect of the c.919G>T (p.Ala307Ser) variant on protein function. Based on the available evidence, the c.919G>T (p.Ala307Ser) variant is classified as 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 |