Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies

Table 3 Allele frequencies and in silico analysis of DMD variants detected in our patients

Genomic variant	cDNA variant	Allele frequency in gnomAD		MutationTaster	Polyphen-2	SIFT	CADD	GERP + + _RS	SpliceAI
Genomic variant	cDNA variant	All populations	Number of hemizygotes	MutationTaster	Polyphen-2	SIFT	CADD	GERP + + _RS	Acceptor Loss	Donor Loss	Acceptor Gain	Donor Gain
g.32519872C > G	c.2380G > C	Absent	Absent	Disease_causing	Possibly damaging	Deleterious	35	5.35	0	0.84 (0 bp)	0	0.17 (7 bp)
g.32383185G > C	c.4977C > G	Absent	Absent	Disease_causing	Probably damaging	Tolerated	27.8	4.62	0	0.44 (− 48 bp)	0	0.91 (5 bp)
g.32366527T > C	c.5444A > G	Absent	Absent	Disease_causing	Probably damaging	Deleterious	34	5.49	0	0.98 (− 4 bp)	0	1.00 (1 bp)
g.32841440A > G	c.329T > C	Absent	Absent	Disease_causing	Probably damaging	Deleterious	26.8	5.68	0	0	0	0
g.32834673T > G	c.442A > C	Absent	Absent	Disease_causing	Probably damaging	Deleterious	25.4	5.51	0	0	0	0
g.32834604C > G	c.511G > C	Absent	Absent	Disease_causing	Probably damaging	Deleterious	25.4	4.65	0	0	0	0
g.32591917C > G	c.1649G > C	Absent	Absent	Disease_causing	Probably damaging	Deleterious	29.5	5.39	0	0	0	0
g.32398712A > G	c.4760T > C	Absent	Absent	Disease_causing	Probably damaging	Deleterious	27.8	5.36	0	0	0	0
g.32381038A > C	c.5192T > G	Absent	Absent	Disease_causing	Possibly damaging	Deleterious	26.6	5.24	0.08 (37 bp)	0	0	0

The cutoff was set to 2.0 for GERP + + _RS (smaller scores indicating less conservation). CADD predicts a continuous phred-like score ranging from 1 to 99; higher scores indicate a more deleterious case. We used the phred-like score cutoff of 20 for CADD

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