Table 1.
Variant ID | Family ID | Phenotype | Genomic variant | cDNA variant | Protein change | Variant type | Zygosity | PhyloP | CADD score | MAF 1000 Genomes | rs# dbsnp | MAF ExAC | MAF EVS6500 | In HGMD |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | #8 | CA plus | chr6:152456368C>T | c.25516-1G>A | -NA- | Splicing | Het | 7.62 | 29.1 | 0 | 0 | 0 | Absent |
2 | #18 | pCA | chr6:152473139C>T | c.24054G>A | p.W8018* | Stopgain SNV | Het | 7.625 | 61 | 0 | 0 | 0 | Absent |
3 | #4 | CA plus | chr6:152473168G>A | c.24025C>T | p.Q8009* | Stopgain SNV | Het | 5.634 | 60 | 0 | 0 | 0 | Absent |
4 | #5, #23 | CA plus | chr6:152476161G>A | c.23782C>T | p.R7928* | Stopgain SNV | Het | 1.316 | 59 | 0 ‖rs570 916267 | 0 | 0 | Absent |
5 | #7 | pCA | chr6:152477125insCAC TCGGCATCAGTGGC ACAGGCGT | c.23684_23685insACG CCTGTGCCACT GATGCCGAGTG | p.C7895* | Frameshift duplication | stopgain | Het | -NA- | 54 | 0 | 0 | 0 | Absent |
6 | #12 | CA plus | chr6:152542097G>T | c.21528C>A | p.Y7176* | Stopgain SNV | Het | 0.153 | 58 | 0 | 0 | 0 | Absent |
7 | #9 | CA plus | chr6:152542688G>A | c.21316C>T | p.Q7106* | Stopgain SNV | Het | 9.038 | 60 | 0 | 0 | 0 | Absent |
8 | #12 | CA plus | chr6:152551729G>A | c.20935C>T | p.R6979* | Stopgain SNV | Het | 1.371 | 41 | 0 | 0 | 0 | Absent |
9 | #14 | CA plus | chr6:152555035G>A | c.20380C>T | p.Q6794* | Stopgain SNV | Het | 9.476 | 60 | 0 | 0 | 0 | Absent |
10 | #23 | CA plus | chr6:152557241C>G | c.G20183 + 1G>C | -NA- | Splicing | Het | 7.808 | 33 | 0 | 0 | 0 | Absent |
11 | #11 | CA plus | chr6:152558041G>A | c.19897C>T | p.Q6633* | Stopgain SNV | Homo | 7.646 | 59 | 0 | 0 | 0 | Absent |
12 | #10 | CA plus | chr6:152558084C>G | c.19855-1G>C | -NA- | Splicing | Homo | 7.304 | 28.1 | 0 | 0 | 0 | Absent |
13 | #19 | CA plus | chr6:152605163G>A | c.17944C>T | p.R5982* | Stopgain SNV | Homo | 1.582 | 50 | 0 | 0 | 0 | Absent |
14 | #14 | CA plus | chr6:152615251insT | c.17480dup | p.Y5827* | Frameshift insertion| stopgain | Het | -NA- | 38 | 0 | 0 | 0 | Absent |
15 | #18 | pCA | chr6:152639275- 152639281 delTCAGTTT | c.16294_16300delA AACTGA | p.K5432Lfs*25 | Frameshift deletion | Het | -NA- | 40 | 0 | 0 | 0 | Absent |
16 | #3 | pCA | chr6:152642966G>A | c.15760C>T | p.R5254* | Stopgain SNV | Homo | 5.373 | 53 | 0 | 0 | 0 | Absent |
17 | #4 | CA plus | chr6:152644651- 152644652delGA | c.15665_15666delTC | p.L5222Hfs*21 | Frameshift deletion | Het | -NA- | 35 | 0 | 0 | 0 | Absent |
18 | #7 | pCA | chr6:152646244T>C | c.15419A>G | p.D5140Gfs1* | (Cryptic) splicing | Het | 3.931 | 19.05 | 0 | 8.2 × 10 −6 | 0 | Absent |
19 | #2 | CA plus | chr6:152651038G>A | c.14569C>T | p.Q4857* | Stopgain SNV | Het | 7.928 | 51 | 0 | 0 | 0 | Absent |
20 | #21 | CA plus | chr6:152651345insA | c.14261dup | p.Q4755Profs*15 | Frameshift insertion | Het | -NA- | 36 | 0 | 0 | 0 | Absent |
21 | #6 | CA plus | chr6:152651352- 152651352delC | c.14255delG | p.G4752Efs*10 | Frameshift deletion | Het | -NA- | 36 | 0 | 0 | 0 | Absent |
22 | #1 | pCA | chr6:152652521- 152652521delG | c.13086delC | p.H4362Qfs*2 | Frameshift deletion | Homo | -NA- | 24.8 | 0 | 0 | 0 | Absent |
23 | #15 | CA plus | chr6:152657975C>T | c.12315 + 1G>A | -NA- | Splicing | Homo | 7.499 | 26.2 | 0 | 0 | 0 | Absent |
24 | #9 | CA plus | chr6:152665320G>A | c.11908C>T | p.R3970* | Stopgain SNV | Het | 6.313 | 51 | 0 | 0 | 0 | Absent |
25 | #5 | CA plus | chr6:152706854insAT | c.8627_8628insAT | p.M2876Ifs*19 | Frameshift insertion | Het | -NA- | 34 | 0 | 0 | 0 | Absent |
26 | #8 | CA plus | chr6:152711589T>C | c.8026-2A>G | -NA- | Splicing | Het | 7.542 | 25.6 | 0 | 0 | 0 | Absent |
27 | #16 | pCA | chr6:152722345C>T | c.6978G>A | p.W2326* | Stopgain SNV | Homo | 5.118 | 20.3 | 0 | 0 | 0 | Absent |
28 | #21 | CA plus | chr6:152737559G>A | c.6034C>T | p.R2012* | Stopgain SNV | Het | 0.595 | 32 | 0.0002 | rs200119679 | 8.2 × 10 −6 | 0 | Absent |
29 | #17 | CA plus | chr6:152765668C>A | c.3736G>T | p.E1246* | Stopgain SNV | Homo | 5.495 | 39 | 0 | 0 | 0 | Absent |
30 | #20 | CA plus | chr6:152776698T>A | c.2776A>T | p.K926* | Stopgain SNV | Het | 3.905 | 36 | 0 | 0 | 0 | Absent |
31 | #22 | CA plus | chr6:152826408G>A | c.727C>T | p.R243* | Stopgain SNV | Homo | 0.771 | 35 | 0 | 0 | 0 | Absent |
32 | #13 | CA plus | chr6:152826453G>A | c.682C>T | p.R228* | Stopgain SNV | Homo | 4.534 | 36 | 0 | 8.2 × 10 −6 | 0 | Absent |
33 | #20 | CA plus | chr6:152826476A>G | c.659T>C | p.F220S | Missense | Het | 9.339 | 28.8 | 0 | 0 | 0 | Absent |
34 | #6 | CA plus | chr6:152832174A>T | c.395T>A | p.L132* | Stopgain SNV | Het | 9.14 | 38 | 0 | 1.6 × 10 −5 | 0 | Absent |
35 | #2 | CA plus | chr6:152841593C>T | c.309 + 1G>A | -NA- | Splicing | Het | 7.187 | 27.8 | 0 | 0 | 0 | Absent |
Genomic positions of the variants according to genome build hg19. DNA changes according to NM_033071.3. Variant type and protein changes according to GVS function based on NP_149062. pCA = pure cerebellar ataxia; CA plus = cerebellar ataxia plus clinical evidence for damage of at least one additional neurological system; PhyloP = PhyloP conservation score based on base-wise conservation across 100 vertebrates; CADD score = scaled Combined Annotation Dependent Depletion score, integrating many diverse annotations into a single measure (C score) for each variant. The predicted pathogenicity of each variant is scored and ranked relative to all ∼8.6 billion single nucleotide variants of the GRCh37/hg19 reference. A scaled CADD score of 20 indicates variants at the top 1%, a CADD score of 30 indicates variants at the top 0.1%, etc. ( Kircher et al. , 2014 ). MAF = minor allele frequency; ExAC= Exome Aggregation Consortium; EVS = Exome Variant Server 6500 exomes all from the NHLBI GO Exome Sequencing Project; HGMD = Human Gene Mutation Database.