Incidental Mutation 'R7336:Wdr62'
| ID |
569489 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Wdr62
|
| Ensembl Gene |
ENSMUSG00000037020 |
| Gene Name |
WD repeat domain 62 |
| Synonyms |
2310038K02Rik |
| MMRRC Submission |
045426-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R7336 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
29939563-29979844 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 29943342 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Glutamine
at position 951
(L951Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000103825
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000108190]
[ENSMUST00000134570]
[ENSMUST00000145027]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000108190
AA Change: L951Q
PolyPhen 2
Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000103825
Gene: ENSMUSG00000037020
AA Change: L951Q
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
27 |
53 |
N/A |
INTRINSIC |
|
WD40
|
101 |
142 |
4.24e-3 |
SMART |
|
WD40
|
145 |
186 |
1.03e-1 |
SMART |
|
WD40
|
189 |
226 |
7.4e0 |
SMART |
|
WD40
|
284 |
322 |
3.55e1 |
SMART |
|
WD40
|
353 |
388 |
1.85e0 |
SMART |
|
WD40
|
395 |
442 |
2.98e-1 |
SMART |
|
WD40
|
482 |
521 |
2.77e-1 |
SMART |
|
WD40
|
524 |
566 |
2.3e0 |
SMART |
|
WD40
|
570 |
610 |
4.18e-2 |
SMART |
|
WD40
|
615 |
657 |
1.54e0 |
SMART |
|
WD40
|
660 |
702 |
8.49e-3 |
SMART |
|
WD40
|
705 |
744 |
3.61e-6 |
SMART |
|
low complexity region
|
763 |
768 |
N/A |
INTRINSIC |
|
low complexity region
|
797 |
811 |
N/A |
INTRINSIC |
|
low complexity region
|
980 |
987 |
N/A |
INTRINSIC |
|
low complexity region
|
1215 |
1226 |
N/A |
INTRINSIC |
|
low complexity region
|
1302 |
1313 |
N/A |
INTRINSIC |
|
low complexity region
|
1477 |
1497 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000134570
AA Change: L483Q
PolyPhen 2
Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000116139
Gene: ENSMUSG00000037020
AA Change: L483Q
| Domain | Start | End | E-Value | Type |
|---|
|
WD40
|
36 |
75 |
2.77e-1 |
SMART |
|
WD40
|
78 |
120 |
2.3e0 |
SMART |
|
WD40
|
124 |
164 |
4.18e-2 |
SMART |
|
WD40
|
169 |
211 |
1.54e0 |
SMART |
|
WD40
|
214 |
256 |
8.49e-3 |
SMART |
|
WD40
|
259 |
298 |
3.61e-6 |
SMART |
|
low complexity region
|
317 |
322 |
N/A |
INTRINSIC |
|
low complexity region
|
351 |
365 |
N/A |
INTRINSIC |
|
low complexity region
|
512 |
519 |
N/A |
INTRINSIC |
|
low complexity region
|
744 |
755 |
N/A |
INTRINSIC |
|
low complexity region
|
831 |
842 |
N/A |
INTRINSIC |
|
low complexity region
|
1006 |
1026 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000145027
AA Change: L951Q
PolyPhen 2
Score 0.929 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000116772
Gene: ENSMUSG00000037020
AA Change: L951Q
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
27 |
53 |
N/A |
INTRINSIC |
|
WD40
|
101 |
142 |
4.24e-3 |
SMART |
|
WD40
|
145 |
186 |
1.03e-1 |
SMART |
|
WD40
|
189 |
226 |
7.4e0 |
SMART |
|
WD40
|
284 |
322 |
3.55e1 |
SMART |
|
WD40
|
353 |
388 |
1.85e0 |
SMART |
|
WD40
|
395 |
442 |
2.98e-1 |
SMART |
|
WD40
|
482 |
521 |
2.77e-1 |
SMART |
|
WD40
|
524 |
566 |
2.3e0 |
SMART |
|
WD40
|
570 |
610 |
4.18e-2 |
SMART |
|
WD40
|
615 |
657 |
1.54e0 |
SMART |
|
WD40
|
660 |
702 |
8.49e-3 |
SMART |
|
WD40
|
705 |
744 |
3.61e-6 |
SMART |
|
low complexity region
|
763 |
768 |
N/A |
INTRINSIC |
|
low complexity region
|
797 |
811 |
N/A |
INTRINSIC |
|
low complexity region
|
980 |
987 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 98.9%
|
| Validation Efficiency |
99% (80/81) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and mental retardation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]
PHENOTYPE: Mice for a hypomorphic allele exhibit reduced brain size due to decreased neural progenitor cells. Cells show spindle instability, spindle assembly checkpoint activation, mitotic arrest and cell death. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 79 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadacl2fm1 |
G |
A |
3: 59,840,174 (GRCm39) |
|
probably null |
Het |
| Abca15 |
A |
T |
7: 119,987,456 (GRCm39) |
Q1247H |
possibly damaging |
Het |
| Acsf2 |
G |
C |
11: 94,462,476 (GRCm39) |
Q180E |
probably benign |
Het |
| Adamts8 |
A |
G |
9: 30,873,363 (GRCm39) |
D856G |
probably benign |
Het |
| Agrn |
A |
T |
4: 156,259,371 (GRCm39) |
C828* |
probably null |
Het |
| Ankub1 |
T |
C |
3: 57,573,108 (GRCm39) |
T205A |
probably benign |
Het |
| Atm |
A |
T |
9: 53,373,803 (GRCm39) |
Y2150N |
possibly damaging |
Het |
| Barhl1 |
A |
G |
2: 28,799,855 (GRCm39) |
F257L |
probably benign |
Het |
| Bcat2 |
T |
A |
7: 45,224,909 (GRCm39) |
C27S |
probably benign |
Het |
| Bod1l |
G |
A |
5: 41,978,867 (GRCm39) |
R816C |
probably damaging |
Het |
| Btg3 |
A |
G |
16: 78,161,695 (GRCm39) |
Y172H |
probably benign |
Het |
| Cacna1d |
T |
C |
14: 29,767,239 (GRCm39) |
D1940G |
probably benign |
Het |
| Catsperg2 |
T |
A |
7: 29,406,026 (GRCm39) |
N624I |
possibly damaging |
Het |
| Ccdc146 |
A |
G |
5: 21,508,110 (GRCm39) |
V646A |
probably benign |
Het |
| Ccp110 |
C |
T |
7: 118,321,433 (GRCm39) |
P363S |
probably damaging |
Het |
| Cct4 |
C |
A |
11: 22,951,564 (GRCm39) |
T377K |
possibly damaging |
Het |
| Cemip2 |
C |
A |
19: 21,803,509 (GRCm39) |
Y847* |
probably null |
Het |
| Cep350 |
T |
A |
1: 155,738,022 (GRCm39) |
H2607L |
probably benign |
Het |
| Cfap46 |
A |
G |
7: 139,200,020 (GRCm39) |
F1954L |
unknown |
Het |
| Chat |
C |
T |
14: 32,145,213 (GRCm39) |
|
probably null |
Het |
| Clasp2 |
A |
G |
9: 113,705,421 (GRCm39) |
|
probably null |
Het |
| Cldn9 |
T |
C |
17: 23,901,989 (GRCm39) |
D212G |
probably benign |
Het |
| Cp |
G |
A |
3: 20,018,696 (GRCm39) |
|
probably null |
Het |
| Cyfip1 |
T |
A |
7: 55,576,148 (GRCm39) |
I1108N |
possibly damaging |
Het |
| Dnah14 |
A |
G |
1: 181,625,299 (GRCm39) |
D4060G |
probably damaging |
Het |
| Dpyd |
A |
G |
3: 118,858,570 (GRCm39) |
T595A |
probably damaging |
Het |
| Eps8 |
G |
A |
6: 137,486,211 (GRCm39) |
R434C |
possibly damaging |
Het |
| Fasl |
A |
G |
1: 161,615,557 (GRCm39) |
Y100H |
probably damaging |
Het |
| Fkbp9 |
A |
T |
6: 56,826,712 (GRCm39) |
N104I |
probably damaging |
Het |
| Frmd4a |
A |
G |
2: 4,478,025 (GRCm39) |
T65A |
possibly damaging |
Het |
| Gm1110 |
T |
C |
9: 26,825,653 (GRCm39) |
N102S |
probably damaging |
Het |
| Gm2381 |
T |
C |
7: 42,471,804 (GRCm39) |
Q25R |
possibly damaging |
Het |
| Gtpbp2 |
A |
G |
17: 46,472,239 (GRCm39) |
Y58C |
probably damaging |
Het |
| H2-T3 |
C |
A |
17: 36,498,237 (GRCm39) |
K269N |
probably damaging |
Het |
| Icosl |
C |
A |
10: 77,909,707 (GRCm39) |
Y217* |
probably null |
Het |
| Il17rd |
G |
T |
14: 26,809,503 (GRCm39) |
R153L |
probably benign |
Het |
| Kif17 |
C |
A |
4: 138,025,617 (GRCm39) |
T973K |
possibly damaging |
Het |
| Klk1b16 |
A |
G |
7: 43,790,907 (GRCm39) |
I236M |
probably benign |
Het |
| Lgmn |
G |
A |
12: 102,389,998 (GRCm39) |
|
probably benign |
Het |
| Lmbr1l |
T |
C |
15: 98,811,468 (GRCm39) |
D54G |
possibly damaging |
Het |
| Lrrc49 |
A |
T |
9: 60,584,474 (GRCm39) |
I196N |
possibly damaging |
Het |
| Maml1 |
C |
T |
11: 50,157,276 (GRCm39) |
A300T |
possibly damaging |
Het |
| Mapkap1 |
A |
T |
2: 34,423,829 (GRCm39) |
Q293L |
possibly damaging |
Het |
| Mki67 |
T |
C |
7: 135,315,568 (GRCm39) |
T69A |
probably benign |
Het |
| Mlph |
G |
A |
1: 90,849,705 (GRCm39) |
|
probably null |
Het |
| Myh1 |
A |
T |
11: 67,111,435 (GRCm39) |
M1625L |
probably benign |
Het |
| Myh3 |
G |
T |
11: 66,981,847 (GRCm39) |
R781L |
probably benign |
Het |
| Nckap5 |
A |
T |
1: 125,953,786 (GRCm39) |
I922K |
probably benign |
Het |
| Nlrp5 |
T |
A |
7: 23,117,059 (GRCm39) |
M261K |
probably damaging |
Het |
| Or1e1d-ps1 |
G |
A |
11: 73,819,663 (GRCm39) |
M204I |
probably benign |
Het |
| Or4f47 |
A |
T |
2: 111,972,514 (GRCm39) |
S75C |
possibly damaging |
Het |
| Or5af1 |
T |
A |
11: 58,722,750 (GRCm39) |
Y257N |
probably damaging |
Het |
| Or8g52 |
A |
G |
9: 39,630,906 (GRCm39) |
N128D |
probably benign |
Het |
| Pak1 |
T |
A |
7: 97,538,179 (GRCm39) |
V262E |
probably benign |
Het |
| Pigw |
A |
T |
11: 84,767,930 (GRCm39) |
D466E |
probably damaging |
Het |
| Pira2 |
A |
T |
7: 3,847,344 (GRCm39) |
L115Q |
probably damaging |
Het |
| Rbm15 |
A |
C |
3: 107,240,432 (GRCm39) |
|
probably benign |
Het |
| Rfx1 |
A |
G |
8: 84,800,385 (GRCm39) |
|
probably benign |
Het |
| Rfx7 |
A |
G |
9: 72,500,639 (GRCm39) |
Y133C |
probably damaging |
Het |
| Serpinb9d |
T |
A |
13: 33,384,702 (GRCm39) |
D226E |
probably benign |
Het |
| Sgk3 |
G |
A |
1: 9,954,701 (GRCm39) |
A271T |
possibly damaging |
Het |
| Sh2d5 |
T |
A |
4: 137,984,150 (GRCm39) |
C173S |
probably benign |
Het |
| Skint8 |
T |
C |
4: 111,796,769 (GRCm39) |
V291A |
probably benign |
Het |
| Slc22a27 |
T |
A |
19: 7,904,054 (GRCm39) |
N28Y |
probably benign |
Het |
| Slc25a54 |
G |
A |
3: 109,023,751 (GRCm39) |
V449I |
probably benign |
Het |
| Slc39a9 |
T |
C |
12: 80,726,316 (GRCm39) |
F255S |
probably damaging |
Het |
| Spata31d1c |
C |
T |
13: 65,183,942 (GRCm39) |
H495Y |
probably damaging |
Het |
| Stab2 |
G |
A |
10: 86,805,049 (GRCm39) |
Q310* |
probably null |
Het |
| Supt16 |
C |
A |
14: 52,408,948 (GRCm39) |
A809S |
possibly damaging |
Het |
| Tenm3 |
A |
T |
8: 48,689,212 (GRCm39) |
M2125K |
possibly damaging |
Het |
| Tex2 |
G |
A |
11: 106,439,685 (GRCm39) |
T565M |
unknown |
Het |
| Tll1 |
G |
A |
8: 64,478,176 (GRCm39) |
A859V |
probably damaging |
Het |
| Tmem106c |
C |
T |
15: 97,867,512 (GRCm39) |
T232I |
possibly damaging |
Het |
| Trim65 |
T |
G |
11: 116,019,116 (GRCm39) |
D141A |
probably benign |
Het |
| Trim80 |
T |
C |
11: 115,332,042 (GRCm39) |
F78S |
probably damaging |
Het |
| Txnrd1 |
T |
A |
10: 82,709,051 (GRCm39) |
I83N |
probably benign |
Het |
| Vnn3 |
G |
A |
10: 23,727,806 (GRCm39) |
G72D |
probably benign |
Het |
| Wasl |
G |
T |
6: 24,619,686 (GRCm39) |
P278Q |
unknown |
Het |
| Zfp760 |
C |
T |
17: 21,942,814 (GRCm39) |
T663I |
unknown |
Het |
|
| Other mutations in Wdr62 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00094:Wdr62
|
APN |
7 |
29,942,948 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00428:Wdr62
|
APN |
7 |
29,970,177 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00579:Wdr62
|
APN |
7 |
29,967,320 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00709:Wdr62
|
APN |
7 |
29,941,486 (GRCm39) |
missense |
probably benign |
0.05 |
|
IGL00924:Wdr62
|
APN |
7 |
29,942,231 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00924:Wdr62
|
APN |
7 |
29,964,643 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00956:Wdr62
|
APN |
7 |
29,960,764 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL01016:Wdr62
|
APN |
7 |
29,953,676 (GRCm39) |
missense |
probably benign |
0.39 |
|
IGL01118:Wdr62
|
APN |
7 |
29,942,206 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL01458:Wdr62
|
APN |
7 |
29,941,187 (GRCm39) |
missense |
probably benign |
0.08 |
|
IGL01977:Wdr62
|
APN |
7 |
29,957,526 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02065:Wdr62
|
APN |
7 |
29,942,894 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
IGL02155:Wdr62
|
APN |
7 |
29,962,068 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02260:Wdr62
|
APN |
7 |
29,970,207 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02404:Wdr62
|
APN |
7 |
29,967,298 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02491:Wdr62
|
APN |
7 |
29,942,184 (GRCm39) |
missense |
probably benign |
0.19 |
|
IGL02556:Wdr62
|
APN |
7 |
29,944,709 (GRCm39) |
splice site |
probably null |
|
|
IGL02739:Wdr62
|
APN |
7 |
29,941,885 (GRCm39) |
nonsense |
probably null |
|
|
IGL03387:Wdr62
|
APN |
7 |
29,970,199 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
ivoire
|
UTSW |
7 |
29,971,045 (GRCm39) |
missense |
probably damaging |
1.00 |
|
I0000:Wdr62
|
UTSW |
7 |
29,944,752 (GRCm39) |
missense |
probably benign |
0.03 |
|
R0304:Wdr62
|
UTSW |
7 |
29,942,299 (GRCm39) |
missense |
probably benign |
0.20 |
|
R0371:Wdr62
|
UTSW |
7 |
29,941,583 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R0400:Wdr62
|
UTSW |
7 |
29,940,887 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R0621:Wdr62
|
UTSW |
7 |
29,953,486 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R0634:Wdr62
|
UTSW |
7 |
29,969,599 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R1758:Wdr62
|
UTSW |
7 |
29,967,328 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2205:Wdr62
|
UTSW |
7 |
29,957,574 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R2254:Wdr62
|
UTSW |
7 |
29,967,328 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2255:Wdr62
|
UTSW |
7 |
29,967,328 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2566:Wdr62
|
UTSW |
7 |
29,973,424 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2851:Wdr62
|
UTSW |
7 |
29,960,862 (GRCm39) |
missense |
possibly damaging |
0.70 |
|
R3150:Wdr62
|
UTSW |
7 |
29,971,095 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4355:Wdr62
|
UTSW |
7 |
29,941,673 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4517:Wdr62
|
UTSW |
7 |
29,969,683 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4839:Wdr62
|
UTSW |
7 |
29,970,111 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4839:Wdr62
|
UTSW |
7 |
29,940,890 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5193:Wdr62
|
UTSW |
7 |
29,964,592 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5289:Wdr62
|
UTSW |
7 |
29,967,300 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5306:Wdr62
|
UTSW |
7 |
29,964,688 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R5878:Wdr62
|
UTSW |
7 |
29,940,772 (GRCm39) |
missense |
probably benign |
|
|
R5942:Wdr62
|
UTSW |
7 |
29,942,504 (GRCm39) |
nonsense |
probably null |
|
|
R6051:Wdr62
|
UTSW |
7 |
29,960,809 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R6237:Wdr62
|
UTSW |
7 |
29,941,860 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6727:Wdr62
|
UTSW |
7 |
29,971,045 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7158:Wdr62
|
UTSW |
7 |
29,970,163 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R7208:Wdr62
|
UTSW |
7 |
29,951,761 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7237:Wdr62
|
UTSW |
7 |
29,969,869 (GRCm39) |
splice site |
probably null |
|
|
R7559:Wdr62
|
UTSW |
7 |
29,970,198 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7845:Wdr62
|
UTSW |
7 |
29,964,667 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R7936:Wdr62
|
UTSW |
7 |
29,964,584 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8002:Wdr62
|
UTSW |
7 |
29,951,785 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8347:Wdr62
|
UTSW |
7 |
29,962,128 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R8399:Wdr62
|
UTSW |
7 |
29,957,486 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8954:Wdr62
|
UTSW |
7 |
29,953,454 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9044:Wdr62
|
UTSW |
7 |
29,962,062 (GRCm39) |
missense |
probably benign |
|
|
R9166:Wdr62
|
UTSW |
7 |
29,941,874 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9212:Wdr62
|
UTSW |
7 |
29,942,563 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9748:Wdr62
|
UTSW |
7 |
29,953,466 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
Z1176:Wdr62
|
UTSW |
7 |
29,955,353 (GRCm39) |
missense |
probably benign |
0.00 |
|
Z1186:Wdr62
|
UTSW |
7 |
29,950,184 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- CAGTTGAGCCTGTCTGAGAC -3'
(R):5'- GACTTCACACTGTGTCTGATGTG -3'
Sequencing Primer
(F):5'- TGTCTGAGACAGTCCCTCAAC -3'
(R):5'- CACACTGTGTCTGATGTGTCTGG -3'
|
| Posted On |
2019-09-13 |
Incidental Mutation