Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease

Table 1 Summary of analyzed genes, genetic variants and the associated autosomal dominant (AD) diseases

Characteristics	AD conditions
Characteristics	All*	Severe and early onset**	Severe and early onset, allelic imbalance***
Number of gene–disease associations	394	77	23
Number of AD diseases	390	76	23
Number of genes	353	72	21
Number of genes per AD disease	1–2	1–2	1
AD diseases, %^β
1–1	1.8	9.1	17.4
1–2	13.5	68.8	60.9
2–1	0.5	2.6	4.3
2–2	3.8	19.5	17.4
Number of variants	664	115	30
Number of variants per AD disease	1–16	1–9	1–3
AD variants, %
PubMed articles
> 1 peer-reviewed publication	60.4	67.0	80.0
1 peer-reviewed publication	39.6	33.0	20.0
Variant type
Intron	0.3	-	-
Missense	76.7	80.0	80.0
Nonsense	16.4	14.8	16.7
Splice acceptor	2.4	3.5	-
Splice donor	3.3	1.7	3.3
Synonymous	0.8	-	-
Non-coding transcript exon	0.1	-	-
ClinVar classification
Pathogenic	79.7	83.5	90.0
Pathogenic/likely pathogenic	7.1	8.7	10.0
Likely pathogenic	13.2	7.8	-

*AD conditions with ClinVar pathogenic and likely pathogenic ClinVar variants in ExAC (Additional file 1: Table S2)
**Severe and early onset AD diseases with ClinVar pathogenic and likely pathogenic variants in ExAC (Additional file 1: Table S3)
***Severe and early onset AD diseases with ClinVar pathogenic and likely pathogenic variants in ExAC with some evidence of allelic imbalance (at least one allele was found with < 35% of read support; Additional file 1: Table S3). Nine of these genes have evidence of mosaicism (at least two alleles show signs of somatic origin (allelic imbalance))
^βAge of onset—Severity. Age of onset score 1 means congenital or very early (< 2 years), age of onset score 2 means mostly early (< 18 years) + variable, severity score 1 means severe, significantly reduced mobility or increased mortality in early life, and severity score 2 means severe plus variable expressivity

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