Download EX110_VA073 affected , the other two are healthy

EX116_VA079_trio
EX110_VA073 affected , the other two are healthy
Result files:
/users/GD/projects/HumanDisease/Vall_Hebron/analysis_ediva1.0/ataxia/EX1
16_VA079_trio
Compound inheritance candidate MYH7B
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The compound variants are
o Frameshift indel and a non damaging SNV on one side
o C>T SNP with 35 CADD score [damaging] on the other side
o These two variants may impair the function of MYH7B
MYH7B (Myosin, Heavy Chain 7B, Cardiac Muscle, Beta) is a Protein
Coding gene. Diseases associated with MYH7B include left ventricular
noncompaction LVNC and myotonic disease.
From https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-891 :
o LVNC has been reported in patients with different types of NMDs,
including dystrophinopathy, laminopathy, zaspopathy, myotonic
dystrophy, Barth syndrome, Friedreich ataxia, Charcot-MarieTooth disease, and metabolic and mitochondrial disorders
[27,28].
It shows String connections to ataxia - related genes:
o
Other compound genes
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Gene PLEKHA7 has two damaging SNPs and it is related
http://neurosciencenews.com/mirna-cancer-cell-reprogramming-2491/
to be an importat gene against cancer which could be impaired in this
sample
Recessive candidate MLC1 [variant is actually common]

This candidate is related to ataxia because it is causal for Megalencephalic
Leukoencephalopathy with Subcortical Cysts
o http://www.cell.com/ajhg/abstract/S0002-9297(07)61409-8
o “Megalencephalic leukoencephalopathy with subcortical cysts
(MLC) is an autosomal recessive disorder characterized by
macrocephaly, deterioration of motor functions with ataxia, and
spasticity, eventuating in mental decline. “
 Also in OMIM identified with MLC1 gene and it is characterized by ataxia
o http://www.omim.org/entry/604004
 A familial case of MLC1 mutated in patients with MLC disease
o http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424803/
 The main problem here is the low coverage we have for the affected
patient with a depth of only 6 [all mutated]
 The variant is a nonframeshift insertion, but it is actually common in
exomes around 6% in Europeans non Finnish [0.8% homozygous]
 In our ExAC values it returns ‘0’ because it was not included but in the
ExAC browser it is shown to be > 4% in the population with 233
homozygous in the Non finnish European sample set,
http://exac.broadinstitute.org/variant/22-50502469-AAGCACCCCCACCCCACAGGCCACTCACCTCCCCG
We did not include this because the variant is not of top quality in ExAC set
(VQSR Tranche INDEL 99.00 to 99.50 )
Variants
Chr
Position
Reference
Alteration
Function(Refseq)
Gene(Refseq)
ExonicFunction(Refseq)
dbsnpIdentifier
EurEVSFrequency
TotalEVSFrequency
Eur1000GenomesFrequ
ency
Total1000GenomesFreq
uency
SIFTScore
polyphen2
MutAss
22
50502469
A
AGCACCCCCACC
CCACAGGCCACT
CACCTCCCCG
exonic
MLC1
nonframeshift
insertion
rs11568189
0
0
20
33584197
C
20
33584521
G
20
33588210
G
T
exonic
MYH7B
nonsynonymous
SNV
rs61745051
0.01442531403
0.01031562779
A
exonic
MYH7B
nonsynonymous
SNV
NA
0
0
GGA
exonic
MYH7B
frameshift
insertion
NA
0
0
0
0.01790
0
0
0
NA
NA
NA
0.00519
NA
0.522
1.975
0
NA
0.237
0.69
0
NA
NA
NA
Condel
Cadd1
Cadd2
Eigen_raw
Eigen_Phred
ABB_score
ExAC_adjusted_AF
ExAC_NFE
SimpleTandemRepeatRe
gion
SimpleTandemRepeatLe
ngth
EX116_VA079
DP
REF
ALT
EX118_VA081
DP
REF
ALT
EX117_VA080
DP
REF
ALT
NA
NA
NA
NA
NA
0
0.06
0.06
0.514
7.631988
35
0.368988
4.15695
0.112
0.0119868
0.0179415
0.207
2.012553
16.29
-0.688883
0.831463
0.1123
0.000263002
0.000200142
NA
NA
NA
NA
NA
0
0
0
NA
NA
NA
NA
NA
1/1
6
0
6
0/1
18
13
5
0/1
27
17
9
NA
0/1
97
47
50
0/0
169
168
1
0/1
124
76
48
NA
0/1
47
28
19
0/1
55
29
26
0/0
68
68
0
NA
0/1
46
21
21
0/1
58
31
20
0/0
57
55
0