DUP chr7:72,846,244-74,187,855
CNV summary
Our verdict is Uncertain significance. Variant got ACMG score 0.
CNV gain of the region 7:72,846,244-74,187,855 (1.3 mb), is localized in (7)(q11.23). The region contains protein-coding and important regions. There is complete overlap over established TS gene(s): LIMK1, ELN. There is complete overlap with established TS region(s): dbVar:nssv15119921. However, all these regions lay inside a transcript, the mechanism of pathogenicity is that they probably break it. There are partially covered regions: DUP dbVar:nssv15154518 7:73,287,016-74,728,902 partially (0.6247650646445003) covered by ROI (7:73,287,016-74,728,902) is considered Pathogenic (and 53 more), but no TS genes affected. There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50 (and 16 more) in the affected region.
Genes
TODOClinGen
TODOACMG Results
Pathogenicity Level: Uncertain_significance
Score: 0
Criteria:
- GAIN_1A : 0 pointsRule : Contains protein-coding or other known functionally important elements.Details:The region contains protein-coding genes, for example: EIF4H. The region contains important regions, for example: dbVar:nssv15137072.
- GAIN_2A Beware, not metRule (not met) : Complete overlap; the known pathogenic gain SV is fully contained within the observed copy-number gain.Details:There is complete overlap with established TS region(s): dbVar:nssv15119921. However, all these regions lay inside a transcript, the mechanism of pathogenicity is that they probably break it.
- GAIN_2B Beware, not metRule (not met) : Partial overlap of a known pathogenic gain SV: The observed CNV does NOT contain the TS gene or critical region for this known pathogenic Gain SV OR Unclear if the known causative gene or critical region is affected OR No specific causative gene or critical region has been established for this known pathogenic SV.Details:[DUP dbVar:nssv15154518 7:73,287,016-74,728,902 partially (0.6247650646445003) covered by ROI (7:73,287,016-74,728,902) is considered Pathogenic , DUP dbVar:nssv15126184 7:73,271,719-74,775,327 partially (0.6092924485637214) covered by ROI (7:73,271,719-74,775,327) is considered Pathogenic , DUP dbVar:nssv15150733 7:73,286,522-74,727,918 partially (0.6253201757185395) covered by ROI (7:73,286,522-74,727,918) is considered Pathogenic , DUP dbVar:nssv15151509 7:73,166,840-74,761,099 partially (0.6404329534912457) covered by ROI (7:73,166,840-74,761,099) is considered Pathogenic , DUP dbVar:nssv15146449 7:73,286,412-74,725,240 partially (0.6265126894945052) covered by ROI (7:73,286,412-74,725,240) is considered Pathogenic , DUP TS3:ISCA-37392 7:73,330,452-74,728,172 partially (0.6134304438657242) covered by ROI (7:73,330,452-74,728,172) is considered Pathogenic , DUP dbVar:nssv15146741 7:73,040,501-75,255,046 partially (0.5180996547823593) covered by ROI (7:73,040,501-75,255,046) is considered Pathogenic , DUP dbVar:nssv15151227 7:73,263,260-74,728,902 partially (0.6308470963577736) covered by ROI (7:73,263,260-74,728,902) is considered Pathogenic , DUP dbVar:nssv15147014;nssv15147017 7:73,280,574-74,725,240 partially (0.628021978782639) covered by ROI (7:73,280,574-74,725,240) is considered Pathogenic , DUP dbVar:nssv15777247 7:10,365-159,327,017 which contains ROI (7:10,365-159,327,017) is considered Pathogenic , DUP dbVar:nssv15147556 7:73,286,125-74,732,517 partially (0.6234347258557846) covered by ROI (7:73,286,125-74,732,517) is considered Pathogenic , DUP dbVar:nssv15148877 7:73,280,574-74,779,057 partially (0.6054669956215719) covered by ROI (7:73,280,574-74,779,057) is considered Pathogenic , DUP dbVar:nssv15148173 7:73,175,475-74,740,268 partially (0.6469743921400466) covered by ROI (7:73,175,475-74,740,268) is considered Pathogenic , DUP dbVar:nssv15150793 7:73,245,641-74,728,902 partially (0.6352321000821838) covered by ROI (7:73,245,641-74,728,902) is considered Pathogenic , DUP dbVar:nssv15146175;nssv15148276 7:73,352,304-74,719,013 partially (0.6113605749285327) covered by ROI (7:73,352,304-74,719,013) is considered Pathogenic , DUP dbVar:nssv15147458 7:73,280,574-74,727,989 partially (0.6268292093145366) covered by ROI (7:73,280,574-74,727,989) is considered Pathogenic , DUP dbVar:nssv15146933 7:73,304,281-74,726,374 partially (0.6213201246331991) covered by ROI (7:73,304,281-74,726,374) is considered Pathogenic , DUP dbVar:nssv15148970 7:73,352,304-75,065,728 partially (0.48765045896403925) covered by ROI (7:73,352,304-75,065,728) is considered Pathogenic , DUP dbVar:nssv15146773 7:73,280,574-74,728,722 partially (0.6265119311009648) covered by ROI (7:73,280,574-74,728,722) is considered Pathogenic , DUP dbVar:nssv15167739 7:73,329,980-74,730,726 partially (0.6124422272132135) covered by ROI (7:73,329,980-74,730,726) is considered Pathogenic , DUP dbVar:nssv16215249 7:73,308,984-74,727,502 partially (0.619570565900468) covered by ROI (7:73,308,984-74,727,502) is considered Pathogenic , DUP dbVar:nssv15168013 7:10,704-159,329,842 which contains ROI (7:10,704-159,329,842) is considered Pathogenic , DUP dbVar:nssv15160831 7:73,323,103-74,726,596 partially (0.6161434364118666) covered by ROI (7:73,323,103-74,726,596) is considered Pathogenic , DUP dbVar:nssv18830985 7:73,250,429-74,748,249 partially (0.6258609178673005) covered by ROI (7:73,250,429-74,748,249) is considered Pathogenic , DUP dbVar:nssv15159763 7:73,312,644-74,726,596 partially (0.6189828226134975) covered by ROI (7:73,312,644-74,726,596) is considered Pathogenic , DUP dbVar:nssv15149887 7:73,175,475-74,751,069 partially (0.6425392582099195) covered by ROI (7:73,175,475-74,751,069) is considered Pathogenic , DUP dbVar:nssv15153678 7:73,166,840-75,274,941 partially (0.4843297356246214) covered by ROI (7:73,166,840-75,274,941) is considered Pathogenic , DUP dbVar:nssv15148904 7:73,192,369-74,883,978 partially (0.588485282355438) covered by ROI (7:73,192,369-74,883,978) is considered Pathogenic , DUP dbVar:nssv15128409 7:73,235,973-74,774,225 partially (0.618808231681155) covered by ROI (7:73,235,973-74,774,225) is considered Pathogenic , DUP dbVar:nssv15146013 7:62,977,085-75,415,352 which contains ROI (7:62,977,085-75,415,352) is considered Pathogenic , DUP dbVar:nssv15150228 7:73,278,089-74,740,162 partially (0.6222445801269841) covered by ROI (7:73,278,089-74,740,162) is considered Pathogenic , DUP dbVar:nssv15174166 7:73,192,410-74,738,864 partially (0.6436958357636244) covered by ROI (7:73,192,410-74,738,864) is considered Pathogenic , DUP dbVar:nssv15147012 7:72,649,515-75,361,855 which contains ROI (7:72,649,515-75,361,855) is considered Pathogenic , DUP dbVar:nssv18830970 7:73,304,280-74,727,918 partially (0.6206465407638739) covered by ROI (7:73,304,280-74,727,918) is considered Pathogenic , DUP dbVar:nssv15755212 7:72,893,987-74,365,935 partially (0.8790181446627191) covered by ROI (7:72,893,987-74,365,935) is considered Pathogenic , DUP dbVar:nssv15151508 7:73,286,522-74,655,531 partially (0.6583842765095044) covered by ROI (7:73,286,522-74,655,531) is considered Pathogenic , DUP dbVar:nssv17955880 7:73,303,348-74,718,991 partially (0.6248100686401868) covered by ROI (7:73,303,348-74,718,991) is considered Pathogenic , DUP dbVar:nssv17976654 7:73,352,304-74,628,471 partially (0.654735626293424) covered by ROI (7:73,352,304-74,628,471) is considered Pathogenic , DUP dbVar:nssv15146778 7:72,179,092-79,164,071 which contains ROI (7:72,179,092-79,164,071) is considered Pathogenic , DUP dbVar:nssv15146396 7:73,312,575-74,723,034 partially (0.6205646530668385) covered by ROI (7:73,312,575-74,723,034) is considered Pathogenic , DUP dbVar:nssv15154519 7:73,166,840-74,732,825 partially (0.6519960280590171) covered by ROI (7:73,166,840-74,732,825) is considered Pathogenic , DUP dbVar:nssv15146450 7:73,352,104-74,719,154 partially (0.6113543762115504) covered by ROI (7:73,352,104-74,719,154) is considered Pathogenic , DUP dbVar:nssv15147013 7:72,768,821-74,869,255 which contains ROI (7:72,768,821-74,869,255) is considered Pathogenic , DUP dbVar:nssv15146395 7:73,280,574-74,839,100 partially (0.5821410743227896) covered by ROI (7:73,280,574-74,839,100) is considered Pathogenic , DUP dbVar:nssv15149513 7:73,263,132-74,728,802 partially (0.6309223767969597) covered by ROI (7:73,263,132-74,728,802) is considered Pathogenic , DUP dbVar:nssv15147334 7:72,938,064-74,779,028 partially (0.6788791089885516) covered by ROI (7:72,938,064-74,779,028) is considered Pathogenic , DUP dbVar:nssv16254014 7:73,245,641-74,750,557 partially (0.6260914230428808) covered by ROI (7:73,245,641-74,750,557) is considered Pathogenic , DUP dbVar:nssv15168014 7:44,935-159,333,620 which contains ROI (7:44,935-159,333,620) is considered Pathogenic , DUP dbVar:nssv17976854 7:73,272,914-74,740,732 partially (0.6233347731121979) covered by ROI (7:73,272,914-74,740,732) is considered Pathogenic , DUP dbVar:nssv15147399 7:73,192,369-74,779,057 partially (0.6273993374878993) covered by ROI (7:73,192,369-74,779,057) is considered Pathogenic , DUP dbVar:nssv15147714 7:72,503,227-74,719,013 which contains ROI (7:72,503,227-74,719,013) is considered Pathogenic , DUP dbVar:nssv15152109 7:73,166,840-74,783,503 partially (0.6315577210587487) covered by ROI (7:73,166,840-74,783,503) is considered Pathogenic , DUP dbVar:nssv15147327 7:73,352,303-74,719,008 partially (0.6113630959131634) covered by ROI (7:73,352,303-74,719,008) is considered Pathogenic , DUP dbVar:nssv15161666;nssv15161679 7:43,361-159,327,017 which contains ROI (7:43,361-159,327,017) is considered Pathogenic ]
- GAIN_2D Beware, not metRule (not met) : Smaller than established benign copy-number gain, breakpoint(s) does not interrupt protein-coding genes.Details:Breakpoint probably does interrupt genes EIF4H
- GAIN_2E : 0 pointsRule : Smaller than established benign copy-number gain, breakpoint(s) potentially interrupts protein-coding gene.Details:Contained in established TS region 1000g, DDD:24479, dbVar, DDD:24478, dbVar, dbVar, probably breaking EIF4H
- GAIN_3A : 0 pointsRule : 0–34 genesDetails:There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, BUD23, STX1A, ABHD11, CLDN3, CLDN4, METTL27, TMEM270, EIF4H
Genes affected
EIF4H (overlap type is "five utr_with_cds". 33.07% of coding sequence and 10.73% of exons, reading frame is destroyed.)
Position: chr7-74174356-74197096
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.98
Decipher HI: 0.22
pHaplo:
pTriplo:
LIMK1 (whole gene)
Position: chr7-74083804-74122525
Region Type: GENE
Protein Coding: Yes
clingenHi: NO_EVIDENCE_AVAILABLE
clingenTs: NO_EVIDENCE_AVAILABLE
LoF pLI: 1.0
Decipher HI: 0.20
pHaplo:
pTriplo:
ELN (whole gene)
Position: chr7-74028173-74069907
Region Type: GENE
Protein Coding: Yes
clingenHi: SUFFICIENT_EVIDENCE
clingenHiDisease:MONDO:0008504
clingenTs: NO_EVIDENCE_AVAILABLE
LoF pLI: 7.3e-10
Decipher HI: 0.086
pHaplo:
pTriplo:
TMEM270 (whole gene)
Position: chr7-73861159-73865890
Region Type: GENE
Protein Coding: Yes
LoF pLI: 4.1e-11
Decipher HI:
pHaplo:
pTriplo:
METTL27 (whole gene)
Position: chr7-73834590-73842516
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.8e-12
Decipher HI:
pHaplo:
pTriplo:
CLDN4 (whole gene)
Position: chr7-73830996-73832690
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.00013
Decipher HI: 0.24
pHaplo:
pTriplo:
CLDN3 (whole gene)
Position: chr7-73768997-73770270
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.45
Decipher HI: 0.33
pHaplo:
pTriplo:
ABHD11 (whole gene)
Position: chr7-73736094-73738802
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.9e-8
Decipher HI: 0.77
pHaplo:
pTriplo:
STX1A (whole gene)
Position: chr7-73699210-73719669
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.0
Decipher HI: 0.23
pHaplo:
pTriplo:
BUD23 (whole gene)
Position: chr7-73683597-73698212
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.9e-8
Decipher HI:
pHaplo:
pTriplo:
DNAJC30 (whole gene)
Position: chr7-73680918-73683453
Region Type: GENE
Protein Coding: Yes
LoF pLI: 5.8e-7
Decipher HI: 0.80
pHaplo:
pTriplo:
VPS37D (whole gene)
Position: chr7-73667831-73672110
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.26
Decipher HI: 0.64
pHaplo:
pTriplo:
MLXIPL (whole gene)
Position: chr7-73593202-73624522
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.2e-11
Decipher HI: 0.36
pHaplo:
pTriplo:
TBL2 (whole gene)
Position: chr7-73567537-73578579
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.4e-9
Decipher HI: 0.31
pHaplo:
pTriplo:
BCL7B (whole gene)
Position: chr7-73536356-73557690
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.023
Decipher HI: 0.29
pHaplo:
pTriplo:
BAZ1B (whole gene)
Position: chr7-73440406-73522293
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.0
Decipher HI: 0.24
pHaplo:
pTriplo:
FZD9 (whole gene)
Position: chr7-73433778-73436120
Region Type: GENE
Protein Coding: Yes
LoF pLI: 5.8e-11
Decipher HI: 0.47
pHaplo:
pTriplo:
FKBP6 (whole gene)
Position: chr7-73328161-73358625
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.0000040
Decipher HI: 0.66
pHaplo:
pTriplo:
TRIM50 (whole gene)
Position: chr7-73312536-73328082
Region Type: GENE
Protein Coding: Yes
LoF pLI: 4.9e-10
Decipher HI: 0.56
pHaplo:
pTriplo:
NSUN5 (whole gene)
Position: chr7-73302516-73308826
Region Type: GENE
Protein Coding: Yes
LoF pLI: 1.1e-10
Decipher HI: 0.70
pHaplo:
pTriplo:
SPDYE10 (whole gene)
Position: chr7-73104008-73155431
Region Type: GENE
Protein Coding: Yes
LoF pLI:
Decipher HI:
pHaplo:
pTriplo:
SPDYE9 (whole gene)
Position: chr7-73075972-73086038
Region Type: GENE
Protein Coding: Yes
LoF pLI:
Decipher HI:
pHaplo:
pTriplo:
SPDYE11 (whole gene)
Position: chr7-73047862-73057911
Region Type: GENE
Protein Coding: Yes
LoF pLI:
Decipher HI:
pHaplo:
pTriplo:
SPDYE8 (whole gene)
Position: chr7-73019719-73029766
Region Type: GENE
Protein Coding: Yes
LoF pLI:
Decipher HI:
pHaplo:
pTriplo:
TRIM74 (whole gene)
Position: chr7-72959485-72969466
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.23
Decipher HI: 0.83
pHaplo:
pTriplo:
POM121 (whole gene)
Position: chr7-72925095-72948299
Region Type: GENE
Protein Coding: Yes
LoF pLI: 0.0023
Decipher HI: 0.87
pHaplo:
pTriplo:
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{
"cnvChange": {
"chr": "7",
"start": 72846244,
"end": 74187855,
"svType": "DUP"
},
"annotations": {
"chr": "7",
"start": 72846244,
"end": 74187855,
"svType": "DUP",
"length": 1341611,
"geneGroups": [
"Nucleoporins",
"Tripartite motif family|Ring finger proteins",
"Speedy/RINGO cell cycle regulator family",
"NOP2/Sun RNA methyltransferase family",
"FKBP prolyl isomerases",
"CD molecules|G protein-coupled receptors, Class F frizzled",
"PHD finger proteins|Bromodomain containing|B-WICH chromatin-remodelling complex subunits",
"BAF complex",
"WD repeat domain containing",
"Basic helix-loop-helix proteins",
"ESCRT-I",
"DNAJ (HSP40) heat shock proteins",
"Ribosomal biogenesis factors|7BS DNA/RNA methyltransferases",
"Syntaxins",
"Abhydrolase domain containing",
"Claudins",
"7BS orphan methyltransferases",
"LIM domain containing|PDZ domain containing|LIMK/TESK kinase family",
"RNA binding motif containing|MicroRNA protein coding host genes"
],
"cytobandString": "(7)(q11.23)",
"overlappedGenes": [
{
"id": "NM_022170.2",
"chr": "7",
"start": 74174356,
"end": 74197096,
"regionType": "GENE",
"overlapType": "FIVE_UTR_WITH_CDS",
"coveredFraction": 0.1072961373390558,
"hgncId": 12741,
"geneSummaryLongCarrier": {
"symbol": "EIF4H",
"proteinCoding": true,
"maneSelectEnsemblId": "ENST00000265753.13",
"maneSelectRefSeqId": "NM_022170.2",
"lof_pLI": 0.97545,
"lof_oe_ci_upper": 0.508,
"decipherHi": 0.2178,
"geneGroup": "RNA binding motif containing|MicroRNA protein coding host genes"
},
"overlappedGenePart": {
"cdsBasesLost": 247,
"cdsBasesSize": 747,
"cdsFractionLost": 0.33065595716198126,
"exonsBasesLost": 275,
"exonsBasesSize": 2563,
"exonsFractionLost": 0.1072961373390558,
"lostExons": 2,
"lostExonsRanks": [
0,
1
],
"readingFrameDestroyed": true,
"overlapType": "FIVE_UTR_WITH_CDS",
"numberOfPLpVariantsCovered": 0,
"escapeNmd": false
}
},
{
"id": "NM_002314.4",
"chr": "7",
"start": 74083804,
"end": 74122525,
"regionType": "GENE",
"overlapType": "FULL",
"coveredFraction": 1,
"hgncId": 6613,
"geneSummaryLongCarrier": {
"symbol": "LIMK1",
"proteinCoding": true,
"maneSelectEnsemblId": "ENST00000336180.7",
"maneSelectRefSeqId": "NM_002314.4",
"lof_pLI": 1,
"lof_oe_ci_upper": 0.338,
"decipherHi": 0.1966,
"clingenHi": "NO_EVIDENCE_AVAILABLE",
"clingenTs": "NO_EVIDENCE_AVAILABLE",
"geneGroup": "LIM domain containing|PDZ domain containing|LIMK/TESK kinase family"
},
"overlappedGenePart": {
"cdsBasesLost": 1944,
"cdsBasesSize": 1944,
"cdsFractionLost": 1,
"exonsBasesLost": 3355,
"exonsBasesSize": 3355,
"exonsFractionLost": 1,
"lostExons": 16,
"lostExonsRanks": [
0,
1,
2,
3,
4,
5,
6,
7,
8,
9,
10,
11,
12,
13,
14,
15
],
"readingFrameDestroyed": false,
"overlapType": "FULL",
"numberOfPLpVariantsCovered": 0,
"escapeNmd": false
},
"triploinsufficiencyType": "NO_EVIDENCE_AVAILABLE",
"haploinsufficiencyType": "NO_EVIDENCE_AVAILABLE"
},
{
"id": "NM_000501.4",
"chr": "7",
"start": 74028173,
"end": 74069907,
"regionType": "GENE",
"overlapType": "FULL",
"coveredFraction": 1,
"hgncId": 3327,
"geneSummaryLongCarrier": {
"inheritances": [
"AD"
],
"diseaseAssociations": [
{
"classification": "DEFINITIVE",
"diseaseName": "supravalvular aortic stenosis",
"diseaseId": "MONDO:0008504",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "STRONG",
"diseaseName": "cutis laxa, autosomal dominant 1",
"diseaseId": "MONDO:0007411",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "STRONG",
"diseaseName": "cutis laxa, autosomal dominant 1",
"diseaseId": "MONDO:0007411",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "STRONG",
"diseaseName": "cutis laxa, autosomal dominant 1",
"diseaseId": "MONDO:0007411",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "DEFINITIVE",
"diseaseName": "supravalvular aortic stenosis",
"diseaseId": "MONDO:0008504",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "DEFINITIVE",
"diseaseName": "cutis laxa, autosomal dominant 1",
"diseaseId": "MONDO:0007411",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "SUPPORTIVE",
"diseaseName": "supravalvular aortic stenosis",
"diseaseId": "MONDO:0008504",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "SUPPORTIVE",
"diseaseName": "autosomal dominant cutis laxa",
"diseaseId": "MONDO:0019571",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "STRONG",
"diseaseName": "cutis laxa, autosomal dominant 1",
"diseaseId": "MONDO:0007411",
"inheritanceMode": null,
"source": "GENCC"
},
{
"classification": "STRONG",
"diseaseName": "supravalvular aortic stenosis",
"diseaseId": "MONDO:0008504",
"inheritanceMode": null,
"source": "GENCC"
}
],
"symbol": "ELN",
"proteinCoding": true,
"maneSelectEnsemblId": "ENST00000252034.12",
"maneSelectRefSeqId": "NM_000501.4",
"lof_pLI": 7.2698e-10,
"lof_oe_ci_upper": 0.697,
"decipherHi": 0.0862,
"clingenHi": "SUFFICIENT_EVIDENCE",
"clingenHiDisease": "MONDO:0008504",
"clingenTs": "NO_EVIDENCE_AVAILABLE"
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"oth_AC": 0,
"oth_AF": 0,
"sas_AN": 4068,
"sas_AC": 0,
"sas_AF": 0
}
},
{
"chr": "7",
"start": 74186250,
"end": 74186813,
"gnomadSvEntry": {
"afr_AN": 33656,
"afr_AC": 7,
"afr_AF": 0.000208,
"ami_AN": 842,
"ami_AC": 0,
"ami_AF": 0,
"amr_AN": 12542,
"amr_AC": 1,
"amr_AF": 0.00008,
"asj_AN": 3172,
"asj_AC": 0,
"asj_AF": 0,
"eas_AN": 4032,
"eas_AC": 1,
"eas_AF": 0.000248,
"fin_AN": 6460,
"fin_AC": 2,
"fin_AF": 0.00031,
"mid_AN": 64,
"mid_AC": 0,
"mid_AF": 0,
"nfe_AN": 58758,
"nfe_AC": 3,
"nfe_AF": 0.000051,
"oth_AN": 1552,
"oth_AC": 0,
"oth_AF": 0,
"sas_AN": 4368,
"sas_AC": 0,
"sas_AF": 0
}
}
]
},
"acmg": {
"position": {
"chr": "7",
"start": 72846244,
"end": 74187855
},
"criteria": [
{
"criterium": "GAIN_1A",
"points": 0
},
{
"criterium": "GAIN_2E",
"points": 0
},
{
"criterium": "GAIN_3A",
"points": 0
}
],
"criteriaReports": [
{
"criterium": "GAIN_1A",
"report": "The region contains protein-coding genes, for example: EIF4H. The region contains important regions, for example: dbVar:nssv15137072. "
},
{
"criterium": "GAIN_2A",
"report": "There is complete overlap with established TS region(s): dbVar:nssv15119921. However, all these regions lay inside a transcript, the mechanism of pathogenicity is that they probably break it. "
},
{
"criterium": "GAIN_2B",
"report": "[DUP dbVar:nssv15154518 7:73,287,016-74,728,902 partially (0.6247650646445003) covered by ROI (7:73,287,016-74,728,902) is considered Pathogenic , DUP dbVar:nssv15126184 7:73,271,719-74,775,327 partially (0.6092924485637214) covered by ROI (7:73,271,719-74,775,327) is considered Pathogenic , DUP dbVar:nssv15150733 7:73,286,522-74,727,918 partially (0.6253201757185395) covered by ROI (7:73,286,522-74,727,918) is considered Pathogenic , DUP dbVar:nssv15151509 7:73,166,840-74,761,099 partially (0.6404329534912457) covered by ROI (7:73,166,840-74,761,099) is considered Pathogenic , DUP dbVar:nssv15146449 7:73,286,412-74,725,240 partially (0.6265126894945052) covered by ROI (7:73,286,412-74,725,240) is considered Pathogenic , DUP TS3:ISCA-37392 7:73,330,452-74,728,172 partially (0.6134304438657242) covered by ROI (7:73,330,452-74,728,172) is considered Pathogenic , DUP dbVar:nssv15146741 7:73,040,501-75,255,046 partially (0.5180996547823593) covered by ROI (7:73,040,501-75,255,046) is considered Pathogenic , DUP dbVar:nssv15151227 7:73,263,260-74,728,902 partially (0.6308470963577736) covered by ROI (7:73,263,260-74,728,902) is considered Pathogenic , DUP dbVar:nssv15147014;nssv15147017 7:73,280,574-74,725,240 partially (0.628021978782639) covered by ROI (7:73,280,574-74,725,240) is considered Pathogenic , DUP dbVar:nssv15777247 7:10,365-159,327,017 which contains ROI (7:10,365-159,327,017) is considered Pathogenic , DUP dbVar:nssv15147556 7:73,286,125-74,732,517 partially (0.6234347258557846) covered by ROI (7:73,286,125-74,732,517) is considered Pathogenic , DUP dbVar:nssv15148877 7:73,280,574-74,779,057 partially (0.6054669956215719) covered by ROI (7:73,280,574-74,779,057) is considered Pathogenic , DUP dbVar:nssv15148173 7:73,175,475-74,740,268 partially (0.6469743921400466) covered by ROI (7:73,175,475-74,740,268) is considered Pathogenic , DUP dbVar:nssv15150793 7:73,245,641-74,728,902 partially (0.6352321000821838) covered by ROI (7:73,245,641-74,728,902) is considered Pathogenic , DUP dbVar:nssv15146175;nssv15148276 7:73,352,304-74,719,013 partially (0.6113605749285327) covered by ROI (7:73,352,304-74,719,013) is considered Pathogenic , DUP dbVar:nssv15147458 7:73,280,574-74,727,989 partially (0.6268292093145366) covered by ROI (7:73,280,574-74,727,989) is considered Pathogenic , DUP dbVar:nssv15146933 7:73,304,281-74,726,374 partially (0.6213201246331991) covered by ROI (7:73,304,281-74,726,374) is considered Pathogenic , DUP dbVar:nssv15148970 7:73,352,304-75,065,728 partially (0.48765045896403925) covered by ROI (7:73,352,304-75,065,728) is considered Pathogenic , DUP dbVar:nssv15146773 7:73,280,574-74,728,722 partially (0.6265119311009648) covered by ROI (7:73,280,574-74,728,722) is considered Pathogenic , DUP dbVar:nssv15167739 7:73,329,980-74,730,726 partially (0.6124422272132135) covered by ROI (7:73,329,980-74,730,726) is considered Pathogenic , DUP dbVar:nssv16215249 7:73,308,984-74,727,502 partially (0.619570565900468) covered by ROI (7:73,308,984-74,727,502) is considered Pathogenic , DUP dbVar:nssv15168013 7:10,704-159,329,842 which contains ROI (7:10,704-159,329,842) is considered Pathogenic , DUP dbVar:nssv15160831 7:73,323,103-74,726,596 partially (0.6161434364118666) covered by ROI (7:73,323,103-74,726,596) is considered Pathogenic , DUP dbVar:nssv18830985 7:73,250,429-74,748,249 partially (0.6258609178673005) covered by ROI (7:73,250,429-74,748,249) is considered Pathogenic , DUP dbVar:nssv15159763 7:73,312,644-74,726,596 partially (0.6189828226134975) covered by ROI (7:73,312,644-74,726,596) is considered Pathogenic , DUP dbVar:nssv15149887 7:73,175,475-74,751,069 partially (0.6425392582099195) covered by ROI (7:73,175,475-74,751,069) is considered Pathogenic , DUP dbVar:nssv15153678 7:73,166,840-75,274,941 partially (0.4843297356246214) covered by ROI (7:73,166,840-75,274,941) is considered Pathogenic , DUP dbVar:nssv15148904 7:73,192,369-74,883,978 partially (0.588485282355438) covered by ROI (7:73,192,369-74,883,978) is considered Pathogenic , DUP dbVar:nssv15128409 7:73,235,973-74,774,225 partially (0.618808231681155) covered by ROI (7:73,235,973-74,774,225) is considered Pathogenic , DUP dbVar:nssv15146013 7:62,977,085-75,415,352 which contains ROI (7:62,977,085-75,415,352) is considered Pathogenic , DUP dbVar:nssv15150228 7:73,278,089-74,740,162 partially (0.6222445801269841) covered by ROI (7:73,278,089-74,740,162) is considered Pathogenic , DUP dbVar:nssv15174166 7:73,192,410-74,738,864 partially (0.6436958357636244) covered by ROI (7:73,192,410-74,738,864) is considered Pathogenic , DUP dbVar:nssv15147012 7:72,649,515-75,361,855 which contains ROI (7:72,649,515-75,361,855) is considered Pathogenic , DUP dbVar:nssv18830970 7:73,304,280-74,727,918 partially (0.6206465407638739) covered by ROI (7:73,304,280-74,727,918) is considered Pathogenic , DUP dbVar:nssv15755212 7:72,893,987-74,365,935 partially (0.8790181446627191) covered by ROI (7:72,893,987-74,365,935) is considered Pathogenic , DUP dbVar:nssv15151508 7:73,286,522-74,655,531 partially (0.6583842765095044) covered by ROI (7:73,286,522-74,655,531) is considered Pathogenic , DUP dbVar:nssv17955880 7:73,303,348-74,718,991 partially (0.6248100686401868) covered by ROI (7:73,303,348-74,718,991) is considered Pathogenic , DUP dbVar:nssv17976654 7:73,352,304-74,628,471 partially (0.654735626293424) covered by ROI (7:73,352,304-74,628,471) is considered Pathogenic , DUP dbVar:nssv15146778 7:72,179,092-79,164,071 which contains ROI (7:72,179,092-79,164,071) is considered Pathogenic , DUP dbVar:nssv15146396 7:73,312,575-74,723,034 partially (0.6205646530668385) covered by ROI (7:73,312,575-74,723,034) is considered Pathogenic , DUP dbVar:nssv15154519 7:73,166,840-74,732,825 partially (0.6519960280590171) covered by ROI (7:73,166,840-74,732,825) is considered Pathogenic , DUP dbVar:nssv15146450 7:73,352,104-74,719,154 partially (0.6113543762115504) covered by ROI (7:73,352,104-74,719,154) is considered Pathogenic , DUP dbVar:nssv15147013 7:72,768,821-74,869,255 which contains ROI (7:72,768,821-74,869,255) is considered Pathogenic , DUP dbVar:nssv15146395 7:73,280,574-74,839,100 partially (0.5821410743227896) covered by ROI (7:73,280,574-74,839,100) is considered Pathogenic , DUP dbVar:nssv15149513 7:73,263,132-74,728,802 partially (0.6309223767969597) covered by ROI (7:73,263,132-74,728,802) is considered Pathogenic , DUP dbVar:nssv15147334 7:72,938,064-74,779,028 partially (0.6788791089885516) covered by ROI (7:72,938,064-74,779,028) is considered Pathogenic , DUP dbVar:nssv16254014 7:73,245,641-74,750,557 partially (0.6260914230428808) covered by ROI (7:73,245,641-74,750,557) is considered Pathogenic , DUP dbVar:nssv15168014 7:44,935-159,333,620 which contains ROI (7:44,935-159,333,620) is considered Pathogenic , DUP dbVar:nssv17976854 7:73,272,914-74,740,732 partially (0.6233347731121979) covered by ROI (7:73,272,914-74,740,732) is considered Pathogenic , DUP dbVar:nssv15147399 7:73,192,369-74,779,057 partially (0.6273993374878993) covered by ROI (7:73,192,369-74,779,057) is considered Pathogenic , DUP dbVar:nssv15147714 7:72,503,227-74,719,013 which contains ROI (7:72,503,227-74,719,013) is considered Pathogenic , DUP dbVar:nssv15152109 7:73,166,840-74,783,503 partially (0.6315577210587487) covered by ROI (7:73,166,840-74,783,503) is considered Pathogenic , DUP dbVar:nssv15147327 7:73,352,303-74,719,008 partially (0.6113630959131634) covered by ROI (7:73,352,303-74,719,008) is considered Pathogenic , DUP dbVar:nssv15161666;nssv15161679 7:43,361-159,327,017 which contains ROI (7:43,361-159,327,017) is considered Pathogenic ]"
},
{
"criterium": "GAIN_2D",
"report": "Breakpoint probably does interrupt genes EIF4H"
},
{
"criterium": "GAIN_2E",
"report": "Contained in established TS region 1000g, DDD:24479, dbVar, DDD:24478, dbVar, dbVar, probably breaking EIF4H"
},
{
"criterium": "GAIN_3A",
"report": "There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, BUD23, STX1A, ABHD11, CLDN3, CLDN4, METTL27, TMEM270, EIF4H"
}
],
"criteriaData": [
{
"criterium": "GAIN_1A",
"report": "The region contains protein-coding genes, for example: EIF4H. The region contains important regions, for example: dbVar:nssv15137072. ",
"met": true,
"points": 0
},
{
"criterium": "GAIN_2A",
"report": "There is complete overlap with established TS region(s): dbVar:nssv15119921. However, all these regions lay inside a transcript, the mechanism of pathogenicity is that they probably break it. ",
"met": false,
"points": null
},
{
"criterium": "GAIN_2B",
"report": "[DUP dbVar:nssv15154518 7:73,287,016-74,728,902 partially (0.6247650646445003) covered by ROI (7:73,287,016-74,728,902) is considered Pathogenic , DUP dbVar:nssv15126184 7:73,271,719-74,775,327 partially (0.6092924485637214) covered by ROI (7:73,271,719-74,775,327) is considered Pathogenic , DUP dbVar:nssv15150733 7:73,286,522-74,727,918 partially (0.6253201757185395) covered by ROI (7:73,286,522-74,727,918) is considered Pathogenic , DUP dbVar:nssv15151509 7:73,166,840-74,761,099 partially (0.6404329534912457) covered by ROI (7:73,166,840-74,761,099) is considered Pathogenic , DUP dbVar:nssv15146449 7:73,286,412-74,725,240 partially (0.6265126894945052) covered by ROI (7:73,286,412-74,725,240) is considered Pathogenic , DUP TS3:ISCA-37392 7:73,330,452-74,728,172 partially (0.6134304438657242) covered by ROI (7:73,330,452-74,728,172) is considered Pathogenic , DUP dbVar:nssv15146741 7:73,040,501-75,255,046 partially (0.5180996547823593) covered by ROI (7:73,040,501-75,255,046) is considered Pathogenic , DUP dbVar:nssv15151227 7:73,263,260-74,728,902 partially (0.6308470963577736) covered by ROI (7:73,263,260-74,728,902) is considered Pathogenic , DUP dbVar:nssv15147014;nssv15147017 7:73,280,574-74,725,240 partially (0.628021978782639) covered by ROI (7:73,280,574-74,725,240) is considered Pathogenic , DUP dbVar:nssv15777247 7:10,365-159,327,017 which contains ROI (7:10,365-159,327,017) is considered Pathogenic , DUP dbVar:nssv15147556 7:73,286,125-74,732,517 partially (0.6234347258557846) covered by ROI (7:73,286,125-74,732,517) is considered Pathogenic , DUP dbVar:nssv15148877 7:73,280,574-74,779,057 partially (0.6054669956215719) covered by ROI (7:73,280,574-74,779,057) is considered Pathogenic , DUP dbVar:nssv15148173 7:73,175,475-74,740,268 partially (0.6469743921400466) covered by ROI (7:73,175,475-74,740,268) is considered Pathogenic , DUP dbVar:nssv15150793 7:73,245,641-74,728,902 partially (0.6352321000821838) covered by ROI (7:73,245,641-74,728,902) is considered Pathogenic , DUP dbVar:nssv15146175;nssv15148276 7:73,352,304-74,719,013 partially (0.6113605749285327) covered by ROI (7:73,352,304-74,719,013) is considered Pathogenic , DUP dbVar:nssv15147458 7:73,280,574-74,727,989 partially (0.6268292093145366) covered by ROI (7:73,280,574-74,727,989) is considered Pathogenic , DUP dbVar:nssv15146933 7:73,304,281-74,726,374 partially (0.6213201246331991) covered by ROI (7:73,304,281-74,726,374) is considered Pathogenic , DUP dbVar:nssv15148970 7:73,352,304-75,065,728 partially (0.48765045896403925) covered by ROI (7:73,352,304-75,065,728) is considered Pathogenic , DUP dbVar:nssv15146773 7:73,280,574-74,728,722 partially (0.6265119311009648) covered by ROI (7:73,280,574-74,728,722) is considered Pathogenic , DUP dbVar:nssv15167739 7:73,329,980-74,730,726 partially (0.6124422272132135) covered by ROI (7:73,329,980-74,730,726) is considered Pathogenic , DUP dbVar:nssv16215249 7:73,308,984-74,727,502 partially (0.619570565900468) covered by ROI (7:73,308,984-74,727,502) is considered Pathogenic , DUP dbVar:nssv15168013 7:10,704-159,329,842 which contains ROI (7:10,704-159,329,842) is considered Pathogenic , DUP dbVar:nssv15160831 7:73,323,103-74,726,596 partially (0.6161434364118666) covered by ROI (7:73,323,103-74,726,596) is considered Pathogenic , DUP dbVar:nssv18830985 7:73,250,429-74,748,249 partially (0.6258609178673005) covered by ROI (7:73,250,429-74,748,249) is considered Pathogenic , DUP dbVar:nssv15159763 7:73,312,644-74,726,596 partially (0.6189828226134975) covered by ROI (7:73,312,644-74,726,596) is considered Pathogenic , DUP dbVar:nssv15149887 7:73,175,475-74,751,069 partially (0.6425392582099195) covered by ROI (7:73,175,475-74,751,069) is considered Pathogenic , DUP dbVar:nssv15153678 7:73,166,840-75,274,941 partially (0.4843297356246214) covered by ROI (7:73,166,840-75,274,941) is considered Pathogenic , DUP dbVar:nssv15148904 7:73,192,369-74,883,978 partially (0.588485282355438) covered by ROI (7:73,192,369-74,883,978) is considered Pathogenic , DUP dbVar:nssv15128409 7:73,235,973-74,774,225 partially (0.618808231681155) covered by ROI (7:73,235,973-74,774,225) is considered Pathogenic , DUP dbVar:nssv15146013 7:62,977,085-75,415,352 which contains ROI (7:62,977,085-75,415,352) is considered Pathogenic , DUP dbVar:nssv15150228 7:73,278,089-74,740,162 partially (0.6222445801269841) covered by ROI (7:73,278,089-74,740,162) is considered Pathogenic , DUP dbVar:nssv15174166 7:73,192,410-74,738,864 partially (0.6436958357636244) covered by ROI (7:73,192,410-74,738,864) is considered Pathogenic , DUP dbVar:nssv15147012 7:72,649,515-75,361,855 which contains ROI (7:72,649,515-75,361,855) is considered Pathogenic , DUP dbVar:nssv18830970 7:73,304,280-74,727,918 partially (0.6206465407638739) covered by ROI (7:73,304,280-74,727,918) is considered Pathogenic , DUP dbVar:nssv15755212 7:72,893,987-74,365,935 partially (0.8790181446627191) covered by ROI (7:72,893,987-74,365,935) is considered Pathogenic , DUP dbVar:nssv15151508 7:73,286,522-74,655,531 partially (0.6583842765095044) covered by ROI (7:73,286,522-74,655,531) is considered Pathogenic , DUP dbVar:nssv17955880 7:73,303,348-74,718,991 partially (0.6248100686401868) covered by ROI (7:73,303,348-74,718,991) is considered Pathogenic , DUP dbVar:nssv17976654 7:73,352,304-74,628,471 partially (0.654735626293424) covered by ROI (7:73,352,304-74,628,471) is considered Pathogenic , DUP dbVar:nssv15146778 7:72,179,092-79,164,071 which contains ROI (7:72,179,092-79,164,071) is considered Pathogenic , DUP dbVar:nssv15146396 7:73,312,575-74,723,034 partially (0.6205646530668385) covered by ROI (7:73,312,575-74,723,034) is considered Pathogenic , DUP dbVar:nssv15154519 7:73,166,840-74,732,825 partially (0.6519960280590171) covered by ROI (7:73,166,840-74,732,825) is considered Pathogenic , DUP dbVar:nssv15146450 7:73,352,104-74,719,154 partially (0.6113543762115504) covered by ROI (7:73,352,104-74,719,154) is considered Pathogenic , DUP dbVar:nssv15147013 7:72,768,821-74,869,255 which contains ROI (7:72,768,821-74,869,255) is considered Pathogenic , DUP dbVar:nssv15146395 7:73,280,574-74,839,100 partially (0.5821410743227896) covered by ROI (7:73,280,574-74,839,100) is considered Pathogenic , DUP dbVar:nssv15149513 7:73,263,132-74,728,802 partially (0.6309223767969597) covered by ROI (7:73,263,132-74,728,802) is considered Pathogenic , DUP dbVar:nssv15147334 7:72,938,064-74,779,028 partially (0.6788791089885516) covered by ROI (7:72,938,064-74,779,028) is considered Pathogenic , DUP dbVar:nssv16254014 7:73,245,641-74,750,557 partially (0.6260914230428808) covered by ROI (7:73,245,641-74,750,557) is considered Pathogenic , DUP dbVar:nssv15168014 7:44,935-159,333,620 which contains ROI (7:44,935-159,333,620) is considered Pathogenic , DUP dbVar:nssv17976854 7:73,272,914-74,740,732 partially (0.6233347731121979) covered by ROI (7:73,272,914-74,740,732) is considered Pathogenic , DUP dbVar:nssv15147399 7:73,192,369-74,779,057 partially (0.6273993374878993) covered by ROI (7:73,192,369-74,779,057) is considered Pathogenic , DUP dbVar:nssv15147714 7:72,503,227-74,719,013 which contains ROI (7:72,503,227-74,719,013) is considered Pathogenic , DUP dbVar:nssv15152109 7:73,166,840-74,783,503 partially (0.6315577210587487) covered by ROI (7:73,166,840-74,783,503) is considered Pathogenic , DUP dbVar:nssv15147327 7:73,352,303-74,719,008 partially (0.6113630959131634) covered by ROI (7:73,352,303-74,719,008) is considered Pathogenic , DUP dbVar:nssv15161666;nssv15161679 7:43,361-159,327,017 which contains ROI (7:43,361-159,327,017) is considered Pathogenic ]",
"met": false,
"points": null
},
{
"criterium": "GAIN_2D",
"report": "Breakpoint probably does interrupt genes EIF4H",
"met": false,
"points": null
},
{
"criterium": "GAIN_2E",
"report": "Contained in established TS region 1000g, DDD:24479, dbVar, DDD:24478, dbVar, dbVar, probably breaking EIF4H",
"met": true,
"points": 0
},
{
"criterium": "GAIN_3A",
"report": "There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, BUD23, STX1A, ABHD11, CLDN3, CLDN4, METTL27, TMEM270, EIF4H",
"met": true,
"points": 0
}
],
"report": "CNV gain of the region 7:72,846,244-74,187,855 (1.3 mb), is localized in (7)(q11.23). The region contains protein-coding and important regions. There is complete overlap over established TS gene(s): LIMK1, ELN. There is complete overlap with established TS region(s): dbVar:nssv15119921. However, all these regions lay inside a transcript, the mechanism of pathogenicity is that they probably break it. There are partially covered regions: DUP dbVar:nssv15154518 7:73,287,016-74,728,902 partially (0.6247650646445003) covered by ROI (7:73,287,016-74,728,902) is considered Pathogenic (and 53 more), but no TS genes affected. There are 26 protein coding genes across 21 gene families: ELN, LIMK1, POM121, TRIM74, SPDYE8, SPDYE11, SPDYE9, SPDYE10, NSUN5, TRIM50 (and 16 more) in the affected region. ",
"pathogenicityLevel": "Uncertain_significance",
"score": 0,
"svType": "DUP",
"phenotype": null
}
}