Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias

Cheng, Hao-Ling; Shao, Ya-Ru; Dong, Yi; Dong, Hai-Lin; Yang, Lu; Ma, Yin; Shen, Ying; Wu, Zhi-Ying

doi:10.1186/s40035-021-00264-z

Table 1 Features of variants identified in this study

From: Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias

Gene	Exon	Nucleotide change	Amino acid change	Mutation type	1000 Genomes	ExAc	In-house data
SACS	10	c.7802T > A	p.V2601D	Missense	0	0	0
SACS	10	c.7901A > C	p.D2634A	Missense	0	0	0
SACS	10	c.8000T > C	p.F2667S	Missense	0	0	0
SACS	10	c.8793dupA	p.R2932fs	Insertion	0	0.000008	0
SACS	10	c.10685_10689del	p.F3562fs	Deletion	0	0	0
SACS	10	c.10938_10941del	p.K3646fs	Deletion	0	0	0
SACS	10	c.11274_11276del	p.3758_3759del	Deletion	0	0	0
SACS	10	c.11319_11321del	p.3773_3774del	Deletion	0	0	0
SACS and 5 others	-	chr13:23490196-24866656 del	–	Deletion	0	0	0
SYNE1	5	c.253C > T	p.R85X	Nonsense	0	0.000008	0
SYNE1	10	c.909 + 1G > A	–	Splicing	0	0	0
SYNE1	27	c.3280A > T	p.K1094X	Nonsense	0	0	0
SYNE1	57	c.9158delA	p.E3053fs	Deletion	0	0	0
SYNE1	65	c.10435C > T	p.R3479X	Nonsense	0	0	0
SYNE1	82	c.15817delG	p.E5273fs	Deletion	0	0	0
SYNE1	93	c.17531_17532insTC	p.H5844fs	Insertion	0	0	0
SYNE1	114	c.20837delT	p.L6946fs	Deletion	0	0	0
SYNE1	131	c.23765 + 1G > A	–	Splicing	0	0	0
ADCK3	6	c.812G > A	p.R271H	Missense	0	0.000048	0
ADCK3	7	c.901C > T	p.R301W	Missense	0	0.000033	0
ADCK3	8	c.960delG	p.L320fs	Deletion	0	0.000009	0
ADCK3	10	c.1228C > T	p.R410X	Nonsense	0	0.000017	0
ADCK3	15	c.1793G > A	p.R598H	Missense	0	0.000008	0
ADCK3	15	c.1844dupG	p.S616fs	Insertion	0	0.000082	0
SETX	3	c.128G > A	p.C43Y	Missense	0	0	0
SETX	10	c.4818_4821dupAATT	p.A1608fs	Insertion	0	0	0
SETX	10	c.5267T > C	p.F1756S	Missense	0	0.000009	0
SETX	23	c.7011delT	p.V2337fs	Deletion	0	0	0
SETX	26	c.7364A > G	p.Y2455C	Missense	0	0.000008	0
ANO10	2	c.132dupA	p.D45fs	Insertion	0.000599	0.000441	0
SPTBN2	2	c.73C > T	p.R25C	Missense	0	0	0
SPTBN2	6	c.622G > A	p.G208R	Missense	0	0	0
STUB1	3	c.433A > C	p.K145Q	Missense	0.000599	0.000702	0
STUB1	3	c.433_435delAAG	p.K145del	Deletion	0	0.000017	0
TTPA	4	c.553G > T	p.D185Y	Missense	0.000199	0	0
ATM	20	c.2922_2923insAA	p.S974fs	Insertion	0	0	0
ATM	45	c.6503C > T	p.S2168L	Missense	0.000200	0.000058	0.001754
KIF1C	23	c.2663_2664insGAGGT	p.V888fs	Insertion	0	0	0

Gene	Predicted impact	dbSNP	HGMD	Family Segre-gation	ACMG
Gene	Predicted impact	dbSNP	HGMD	Family Segre-gation	Evidence	Classification
SACS	D/P/D	NA	Novel	NA	PM1,PM2,PP3,PP4	LP
SACS	D/D/A	NA	Novel	Yes	PM1,PM2,PP1,PP3,PP4	LP
SACS	D/D/D	NA	Novel	Yes	PM2,PM3,PP1,PP3,PP4	LP
SACS	NA/NA/NA	rs767871841	Novel	Yes	PVS1,PM2,PP1,PP4	P
SACS	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1,PP4	P
SACS	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P
SACS	NA/NA/NA	rs1454517884	Known	Yes	PM2,PM4,PP1,PP5	LP
SACS	NA/NA/NA	NA	Novel	Yes	PM2,PM4,PP1,PP4	LP
SACS and 5 others	NA/NA/NA	NA	Novel	Yes	1A,2A,3A,4A,5A	P
SYNE1	NA/NA/A	rs768958602	Novel	Yes	PVS1,PM2,PP1,PP3	P
SYNE1	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1,PP3	P
SYNE1	NA/NA/A	NA	Novel	Yes	PVS1,PM2,PM3,PP1	P
SYNE1	NA/NA/NA	NA	Novel	NA	PVS1,PM2	LP
SYNE1	NA/NA/A	NA	Novel	Yes	PVS1,PM2,PP1,PP3	P
SYNE1	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PM3,PP1	P
SYNE1	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PM3,PP1	P
SYNE1	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P
SYNE1	NA/NA/D	NA	Novel	Yes	PVS1,PM2,PP1,PP3	P
ADCK3	D/D/D	rs765859566	Novel	Yes	PM2,PP1,PP3	VUS
ADCK3	D/D/D	rs140246430	Known	Yes	PS1,PM2,PP1,PP3,PP5	LP
ADCK3	NA/NA/NA	rs767164059	Novel	Yes	PVS1,PM2,PP1	P
ADCK3	NA/NA/A	rs753254213	Known	Yes	PVS1,PM2,PP1,PP3,PP5	P
ADCK3	D/D/D	rs766101783	Novel	Yes	PM2,PM3,PP1,PP3	LP
ADCK3	NA/NA/NA	rs863223885	Known	Yes	PVS1,PM2,PP1,PP5	P
SETX	D/D/D	NA	Novel	Yes	PM2,PM3,PP1,PP3	LP
SETX	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P
SETX	D/D/D	rs762175796	Known	Yes	PS1,PM2,PM3,PP1,PP3, PP5	P
SETX	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P
SETX	D/D/D	rs778210918	Novel	NA	PM2,PP3,PP4	VUS
ANO10	NA/NA/NA	rs540331226	Known	Yes	PVS1,PS1,PM2,PP1,PP5	P
SPTBN2	D/D/D	NA	Novel	Yes	PM1,PM2,PP1,PP3	LP
SPTBN2	D/D/D	NA	Novel	Yes	PM1,PM2,PP1,PP3	LP
STUB1	T/P/D	rs146251364	Known	Yes	PS1,PM1,PM2,PP1,PP5	P
STUB1	NA/NA/NA	rs779647632	Known	Yes	PS1,PM2,PM3,PM4,PP1	P
TTPA	D/D/D	rs564501015	Novel	Yes	PM1,PM2,PP1,PP3	LP
ATM	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P
ATM	D/D/D	rs200431631	Known	Yes	PM1,PM2,PM3,PP1,PP5	LP
KIF1C	NA/NA/NA	NA	Novel	Yes	PVS1,PM2,PP1	P

In-house data: n = 2000. The impact of non-synonymous protein-coding region variants was determined using prediction software including SIFT, PolyPhen-2 and Mutation Taste. SIFT results as Tolerated (T) or Deleterious (D). PolyPhen-2 results as Unknown (UN), Benign (B), Possibly Damaging (P) or Probably Damaging (D). Mutation Taste results as Tolerated (T), Disease causing (D) and Disease causing automatic (A). NA, Not available. ACMG, American College of Medical Genetics. ACMG evidence by reference to the ACMG standards and guidelines. ACMG classification including Pathogenic (P), Likely pathogenic (LP) and Uncertain significance (VUS)

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ISSN: 2047-9158

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