7:72846244-74187855 DEL

CNV summary

Our verdict is Pathogenic. Variant got ACMG score 1.45.

CNV loss 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 with established HI region(s): dbVar:nssv17955650, dbVar:nssv17971140 (and 21 more). Among those, regions with breakpoints not laying inside the transcripts: dbVar:nssv17955650, dbVar:nssv15128343 (and 6 more). There are 26 protein coding genes across 21 gene families: ELN, LIMK1, BAZ1B, EIF4H, MLXIPL, CLDN3, CLDN4, TRIM50, VPS37D, STX1A (and 16 more) in the affected region.

Genes

ABHD11 BAZ1B BCL7B BUD23 CLDN3 CLDN4 DNAJC30 EIF4H ELN FKBP6 FZD9 LIMK1 METTL27 MLXIPL NSUN5 POM121 SPDYE10 SPDYE11 SPDYE8 SPDYE9 STX1A TBL2 TMEM270 TRIM50 TRIM74 VPS37D

ClinGen

TODO

Variant links:

ACMG Results

Pathogenicity Level: Pathogenic

Score: 1.45

Criteria:

LOSS_1A : 0 points
Rule : Contains protein-coding or other known functionally important elements.
Details:
The region contains protein-coding genes, for example: POM121. The region contains important regions, for example: dbVar:nssv17955650.
LOSS_2A : 1 points
Rule : Complete overlap of a known pathogenic Loss SV.
Details:
There is complete overlap with established HI region(s): dbVar:nssv17955650, dbVar:nssv17971140, dbVar:nssv15128343, dbVar:nssv15130113, dbVar:nssv15147201, morbid:DNAJC30, dbVar:nssv15140244, dbVar:nssv15130169, morbid:ELN, dbVar:nssv15770120, dbVar:nssv16214500, dbVar:nssv15167740, dbVar:nssv16208140, HI3:ELN, dbVar:nssv16213814, dbVar:nssv18791884, dbVar:nssv18791887, morbid:FKBP6, dbVar:nssv15137072, dbVar:nssv15128578, dbVar:nssv18786274, dbVar:nssv16214480, dbVar:nssv17172746. Among those, regions with breakpoints not laying inside the transcripts: dbVar:nssv17955650, dbVar:nssv15128343, morbid:DNAJC30, morbid:ELN, dbVar:nssv16208140, HI3:ELN, morbid:FKBP6, dbVar:nssv15137072.
LOSS_3B : 0.45 points
Rule : 25–34 genes
Details:
There are 26 protein coding genes across 21 gene families: ELN, LIMK1, BAZ1B, EIF4H, MLXIPL, CLDN3, CLDN4, TRIM50, VPS37D, STX1A, POM121, FZD9, BUD23, TRIM74, NSUN5, BCL7B, FKBP6, DNAJC30, TBL2, ABHD11, METTL27, TMEM270, SPDYE10, SPDYE9, SPDYE11, SPDYE8

Overlapped Genes

List of MANE transcripts overlapped by the CNV.

Gene	Overlap (% CDS)	Scores	ClinGen Dosage	Dosage (p)	Top Disease Association
ABHD11 HGNC: 16407	Internal 100% CDS covered	LoF pLI: 1.8683e-8 DECIPHER: 0.7655	HI:N/A TS:N/A	Haplo: 0.10 Triplo: 0.36	N/A
BAZ1B HGNC: 961	Internal 100% CDS covered	LoF pLI: 1 DECIPHER: 0.2374	HI:N/A TS:N/A	Haplo: 0.99 Triplo: 1.00	autism spectrum disorder Limited AD
BCL7B HGNC: 1005	Internal 100% CDS covered	LoF pLI: 0.023124 DECIPHER: 0.2863	HI:N/A TS:N/A	Haplo: 0.14 Triplo: 0.67	N/A
BUD23 HGNC: 16405	Internal 100% CDS covered	LoF pLI: 1.8804e-8 DECIPHER: N/A	HI:N/A TS:N/A	Haplo: 0.20 Triplo: 0.34	N/A
CLDN3 HGNC: 2045	Partial_last_exon 100% CDS covered	LoF pLI: 0.45321 DECIPHER: 0.3346	HI:N/A TS:N/A	Haplo: 0.54 Triplo: 0.48	N/A
CLDN4 HGNC: 2046	Partial_last_exon 100% CDS covered	LoF pLI: 0.00012713 DECIPHER: 0.2372	HI:N/A TS:N/A	Haplo: 0.42 Triplo: 0.24	N/A
DNAJC30 HGNC: 16410	Partial_last_exon 100% CDS covered	LoF pLI: 5.8209e-7 DECIPHER: 0.8016	HI:N/A TS:N/A	Haplo: 0.12 Triplo: 0.67	Leber hereditary optic neuropathy (+2) Supportive Mitochondrial
EIF4H HGNC: 12741	Five_utr_with_cds 33% CDS covered	LoF pLI: 0.97545 DECIPHER: 0.2178	HI:N/A TS:N/A	Haplo: 0.66 Triplo: 0.95	N/A
ELN HGNC: 3327	Internal 100% CDS covered	LoF pLI: 7.2698e-10 DECIPHER: 0.0862	HI: SUFFICIENT_EVIDENCE TS: NO_EVIDENCE_AVAILABLE	Haplo: 0.44 Triplo: 0.63	cutis laxa, autosomal dominant 1 (+9) Strong AD
FKBP6 HGNC: 3722	Internal 100% CDS covered	LoF pLI: 0.0000039823 DECIPHER: 0.6569	HI:N/A TS:N/A	Haplo: 0.14 Triplo: 0.31	spermatogenic failure 77 Moderate AR
FZD9 HGNC: 4047	Partial_last_exon 100% CDS covered	LoF pLI: 5.8105e-11 DECIPHER: 0.4695	HI:N/A TS:N/A	Haplo: 0.21 Triplo: 0.37	N/A
LIMK1 HGNC: 6613	Internal 100% CDS covered	LoF pLI: 1 DECIPHER: 0.1966	HI: NO_EVIDENCE_AVAILABLE TS: NO_EVIDENCE_AVAILABLE	Haplo: 0.65 Triplo: 0.95	N/A
METTL27 HGNC: 19068	Internal 100% CDS covered	LoF pLI: 1.7608e-12 DECIPHER: N/A	HI:N/A TS:N/A	Haplo: 0.07 Triplo: 0.19	N/A
MLXIPL HGNC: 12744	Internal 100% CDS covered	LoF pLI: 1.1896e-11 DECIPHER: 0.3645	HI:N/A TS:N/A	Haplo: 0.61 Triplo: 0.69	N/A
NSUN5 HGNC: 16385	Internal 100% CDS covered	LoF pLI: 1.1208e-10 DECIPHER: 0.7014	HI:N/A TS:N/A	Haplo: 0.15 Triplo: 0.70	N/A
POM121 HGNC: 19702	Internal 100% CDS covered	LoF pLI: 0.0022511 DECIPHER: 0.8675	HI:N/A TS:N/A	Haplo: 0.21 Triplo: 0.58	N/A
SPDYE10 HGNC: 51506	Internal 100% CDS covered	LoF pLI: N/A DECIPHER: N/A	HI:N/A TS:N/A	Haplo: N/A Triplo: N/A	N/A
SPDYE11 HGNC: 51507	Internal 100% CDS covered	LoF pLI: N/A DECIPHER: N/A	HI:N/A TS:N/A	Haplo: N/A Triplo: N/A	N/A
SPDYE8 HGNC: 33771	Internal 100% CDS covered	LoF pLI: N/A DECIPHER: N/A	HI:N/A TS:N/A	Haplo: N/A Triplo: N/A	N/A
SPDYE9 HGNC: 45034	Internal 100% CDS covered	LoF pLI: N/A DECIPHER: N/A	HI:N/A TS:N/A	Haplo: N/A Triplo: N/A	N/A
STX1A HGNC: 11433	Internal 100% CDS covered	LoF pLI: 0.99999 DECIPHER: 0.2282	HI:N/A TS:N/A	Haplo: 0.32 Triplo: 0.56	cystic fibrosis (+2) Supportive AR
TBL2 HGNC: 11586	Internal 100% CDS covered	LoF pLI: 1.3589e-9 DECIPHER: 0.3081	HI:N/A TS:N/A	Haplo: 0.11 Triplo: 0.34	N/A
TMEM270 HGNC: 23018	Internal 100% CDS covered	LoF pLI: 4.0928e-11 DECIPHER: N/A	HI:N/A TS:N/A	Haplo: 0.04 Triplo: 0.05	N/A
TRIM50 HGNC: 19017	Internal 100% CDS covered	LoF pLI: 4.8695e-10 DECIPHER: 0.5555	HI:N/A TS:N/A	Haplo: 0.39 Triplo: 0.63	N/A
TRIM74 HGNC: 17453	Internal 100% CDS covered	LoF pLI: 0.22669 DECIPHER: 0.8314	HI:N/A TS:N/A	Haplo: 0.19 Triplo: 0.54	N/A
VPS37D HGNC: 18287	Internal 100% CDS covered	LoF pLI: 0.26255 DECIPHER: 0.6411	HI:N/A TS:N/A	Haplo: 0.32 Triplo: 0.54	N/A

gnomAD Structural Variants

No gnomAD SVs Found

This CNV does not overlap any gnomad svs.

ClinVar Structural Variants

Variation ID	Size	Overlap	Type	Clinical Significance	Position
7:54185-159282390	159.2 Mb	Internal 0.8%	DEL	Pathogenic See cases	7:54,185-159,282,390
7:62736364-75432710	12.7 Mb	Internal 10.6%	DEL	Pathogenic See cases	7:62,736,364-75,432,710
7:62977085-75415352	12.4 Mb	Internal 10.8%	DUP	Pathogenic See cases	7:62,977,085-75,415,352
7:68668307-73710276	5.0 Mb	Partial 17.1%	DEL	Pathogenic See cases	7:68,668,307-73,710,276
7:69382353-77823832	8.4 Mb	Internal 15.9%	DEL	Pathogenic See cases	7:69,382,353-77,823,832
7:71148562-72895414	1.7 Mb	Partial 2.8%	DEL	Uncertain significance See cases	7:71,148,562-72,895,414
7:71225344-81735657	10.5 Mb	Internal 12.8%	DEL	Pathogenic See cases	7:71,225,344-81,735,657
7:71461127-73614730	2.2 Mb	Partial 35.7%	DEL	Pathogenic See cases	7:71,461,127-73,614,730
7:71478043-73444574	2.0 Mb	Partial 30.4%	DEL	Uncertain significance See cases	7:71,478,043-73,444,574
7:72179092-79164071	7.0 Mb	Internal 19.2%	DUP	Likely pathogenic See cases	7:72,179,092-79,164,071
7:72649515-75361855	2.7 Mb	Internal 49.5%	DUP	Pathogenic See cases	7:72,649,515-75,361,855
7:72768821-74869255	2.1 Mb	Internal 63.9%	DUP	Pathogenic See cases	7:72,768,821-74,869,255
7:72930548-74869255	1.9 Mb	Partial 64.9%	DEL	Pathogenic See cases	7:72,930,548-74,869,255
7:72938064-74779028	1.8 Mb	Partial 67.9%	DUP	Pathogenic See cases	7:72,938,064-74,779,028
7:73040501-75255046	2.2 Mb	Partial 51.8%	DUP	Uncertain significance See cases	7:73,040,501-75,255,046
7:73040501-75255046	2.2 Mb	Partial 51.8%	DUP	Pathogenic See cases	7:73,040,501-75,255,046
7:73096542-74727989	1.6 Mb	Partial 66.9%	DEL	Pathogenic See cases	7:73,096,542-74,727,989
7:73175475-74740268	1.6 Mb	Partial 64.7%	DUP	Pathogenic See cases	7:73,175,475-74,740,268
7:73192369-74779057	1.6 Mb	Partial 62.7%	DUP	Pathogenic See cases	7:73,192,369-74,779,057
7:73192369-74779057	1.6 Mb	Partial 62.7%	DEL	Pathogenic See cases	7:73,192,369-74,779,057
7:73192369-74869255	1.7 Mb	Partial 59.4%	DEL	Pathogenic See cases	7:73,192,369-74,869,255
7:73192369-74883978	1.7 Mb	Partial 58.8%	DUP	Pathogenic See cases	7:73,192,369-74,883,978
7:73214501-74773500	1.6 Mb	Partial 62.4%	DEL	Pathogenic Williams syndrome	7:73,214,501-74,773,500
7:73229597-74727852	1.5 Mb	Partial 64%	DEL	Pathogenic Williams syndrome	7:73,229,597-74,727,852
7:73247356-74727974	1.5 Mb	Partial 63.5%	DUP	Pathogenic 7q11.23 microduplication syndrome	7:73,247,356-74,727,974
7:73271690-74727989	1.5 Mb	Partial 62.9%	DEL	Pathogenic See cases	7:73,271,690-74,727,989
7:73280574-74723034	1.4 Mb	Partial 62.9%	DEL	Pathogenic See cases	7:73,280,574-74,723,034
7:73280574-74725240	1.4 Mb	Partial 62.8%	DUP	Pathogenic See cases	7:73,280,574-74,725,240
7:73280574-74725240	1.4 Mb	Partial 62.8%	DUP	Pathogenic See cases	7:73,280,574-74,725,240
7:73280574-74727918	1.4 Mb	Partial 62.7%	DEL	Pathogenic See cases	7:73,280,574-74,727,918
7:73280574-74727989	1.4 Mb	Partial 62.7%	DUP	Pathogenic See cases	7:73,280,574-74,727,989
7:73280574-74728722	1.4 Mb	Partial 62.7%	DUP	Pathogenic See cases	7:73,280,574-74,728,722
7:73280574-74779057	1.5 Mb	Partial 60.5%	DUP	Pathogenic See cases	7:73,280,574-74,779,057
7:73280574-74789341	1.5 Mb	Partial 60.1%	DEL	Pathogenic See cases	7:73,280,574-74,789,341
7:73280574-74839100	1.6 Mb	Partial 58.2%	DUP	Pathogenic See cases	7:73,280,574-74,839,100
7:73280574-74924007	1.6 Mb	Partial 55.2%	DEL	Pathogenic See cases	7:73,280,574-74,924,007
7:73286125-74732517	1.4 Mb	Partial 62.3%	DUP	Pathogenic See cases	7:73,286,125-74,732,517
7:73286412-73556222	269.8 kb	Full 100%	DEL	Uncertain significance See cases	7:73,286,412-73,556,222
7:73286412-74707848	1.4 Mb	Partial 63.4%	DEL	Pathogenic See cases	7:73,286,412-74,707,848
7:73286412-74723034	1.4 Mb	Partial 62.7%	DEL	Pathogenic See cases	7:73,286,412-74,723,034
7:73286412-74725240	1.4 Mb	Partial 62.7%	DUP	Pathogenic See cases	7:73,286,412-74,725,240
7:73286412-74725240	1.4 Mb	Partial 62.7%	DEL	Pathogenic See cases	7:73,286,412-74,725,240
7:73286412-74727989	1.4 Mb	Partial 62.5%	DEL	Pathogenic See cases	7:73,286,412-74,727,989
7:73286412-74758583	1.5 Mb	Partial 61.2%	DEL	Pathogenic See cases	7:73,286,412-74,758,583
7:73286412-74779057	1.5 Mb	Partial 60.4%	DEL	Pathogenic See cases	7:73,286,412-74,779,057
7:73286412-74869255	1.6 Mb	Partial 57%	DEL	Pathogenic See cases	7:73,286,412-74,869,255
7:73286508-74727852	1.4 Mb	Partial 62.5%	DEL	Pathogenic See cases	7:73,286,508-74,727,852
7:73286522-74727156	1.4 Mb	Partial 62.6%	DEL	Pathogenic See cases	7:73,286,522-74,727,156
7:73302466-74798315	1.5 Mb	Partial 59.2%	DEL	Pathogenic not provided	7:73,302,466-74,798,315
7:73303398-74735532	1.4 Mb	Partial 61.8%	DEL	Likely pathogenic Williams syndrome	7:73,303,398-74,735,532
7:73304255-74718954	1.4 Mb	Partial 62.5%	DEL	Pathogenic See cases	7:73,304,255-74,718,954
7:73304277-74727414	1.4 Mb	Partial 62.1%	DEL	Pathogenic Williams syndrome	7:73,304,277-74,727,414
7:73304280-74727852	1.4 Mb	Partial 62.1%	DEL	Pathogenic See cases	7:73,304,280-74,727,852
7:73312575-74723034	1.4 Mb	Partial 62.1%	DUP	Pathogenic See cases	7:73,312,575-74,723,034
7:73312582-74725057	1.4 Mb	Partial 62%	DEL	Pathogenic See cases	7:73,312,582-74,725,057
7:73312644-74726596	1.4 Mb	Partial 61.9%	DUP	Pathogenic Schizophrenia	7:73,312,644-74,726,596
7:73323103-74726596	1.4 Mb	Partial 61.6%	DUP	Pathogenic Autism	7:73,323,103-74,726,596
7:73324677-73352304	27.6 kb	Full 100%	DUP	Benign See cases	7:73,324,677-73,352,304
7:73330453-74728172	1.4 Mb	Partial 61.3%	DEL	Pathogenic not provided	7:73,330,453-74,728,172
7:73352104-74719154	1.4 Mb	Partial 61.1%	DUP	Pathogenic See cases	7:73,352,104-74,719,154
7:73352104-74719154	1.4 Mb	Partial 61.1%	DEL	Pathogenic See cases	7:73,352,104-74,719,154
7:73352303-74719008	1.4 Mb	Partial 61.1%	DUP	Pathogenic See cases	7:73,352,303-74,719,008
7:73352303-74719008	1.4 Mb	Partial 61.1%	DEL	Pathogenic See cases	7:73,352,303-74,719,008
7:73352303-74779051	1.4 Mb	Partial 58.6%	DEL	Pathogenic See cases	7:73,352,303-74,779,051
7:73352303-74924023	1.6 Mb	Partial 53.2%	DEL	Pathogenic See cases	7:73,352,303-74,924,023
7:73352304-74719013	1.4 Mb	Partial 61.1%	DUP	Pathogenic See cases	7:73,352,304-74,719,013
7:73352304-74719013	1.4 Mb	Partial 61.1%	DEL	Pathogenic See cases	7:73,352,304-74,719,013
7:73352304-74719013	1.4 Mb	Partial 61.1%	DUP	Pathogenic See cases	7:73,352,304-74,719,013
7:73352304-74719013	1.4 Mb	Partial 61.1%	DEL	Pathogenic See cases	7:73,352,304-74,719,013
7:73352304-74869255	1.5 Mb	Partial 55.1%	DEL	Pathogenic See cases	7:73,352,304-74,869,255
7:73352304-74924037	1.6 Mb	Partial 53.2%	DEL	Pathogenic See cases	7:73,352,304-74,924,037
7:73352304-74924037	1.6 Mb	Partial 53.2%	DEL	Pathogenic See cases	7:73,352,304-74,924,037
7:73352304-75065728	1.7 Mb	Partial 48.8%	DUP	Pathogenic See cases	7:73,352,304-75,065,728
7:73352304-76722261	3.4 Mb	Partial 24.8%	DEL	Pathogenic See cases	7:73,352,304-76,722,261
7:73614671-73942928	328.3 kb	Full 100%	DEL	Pathogenic See cases	7:73,614,671-73,942,928
7:73755813-74133404	377.6 kb	Full 100%	DUP	Uncertain significance See cases	7:73,755,813-74,133,404
7:73755831-74131326	375.5 kb	Full 100%	DEL	Pathogenic See cases	7:73,755,831-74,131,326
7:73873420-83988860	10.1 Mb	Partial 3.1%	DEL	Pathogenic See cases	7:73,873,420-83,988,860
7:74030000-74062163	32.2 kb	Full 100%	DEL	Pathogenic Supravalvar aortic stenosis	7:74,030,000-74,062,163
7:74031409-74104712	73.3 kb	Full 100%	DUP	Likely benign See cases	7:74,031,409-74,104,712
7:74035344-74068720	33.4 kb	Full 100%	DEL	Pathogenic Supravalvar aortic stenosis	7:74,035,344-74,068,720
7:74035454-74133404	98.0 kb	Full 100%	DUP	Pathogenic See cases	7:74,035,454-74,133,404
7:74047652-74924037	876.4 kb	Partial 16%	DEL	Pathogenic See cases	7:74,047,652-74,924,037
7:74053426-75069953	1.0 Mb	Partial 13.2%	DUP	Likely benign See cases	7:74,053,426-75,069,953
7:74059907-74059960	53 bp	Full 100%	DEL	Benign/Likely benign not provided\|Supravalvar aortic stenosis	7:74,059,907-74,059,960
7:74068647-74068710	63 bp	Full 100%	DEL	Likely pathogenic Supravalvar aortic stenosis	7:74,068,647-74,068,710
7:74163876-74593260	429.4 kb	Partial 5.6%	DUP	Uncertain significance See cases	7:74,163,876-74,593,260
7:74176025-75361855	1.2 Mb	Partial 1%	DEL	Pathogenic See cases	7:74,176,025-75,361,855
7:74177663-74718954	541.3 kb	Partial 1.9%	DEL	Uncertain significance See cases	7:74,177,663-74,718,954

ClinGen Recurrent CNVs

Region Name	Size	Overlap	Type	Position
LCR-C_cen	134.5 kb	Full 100%	N/A	7:72,859,312-72,993,773
LCR-A_cen	160.2 kb	Full 100%	N/A	7:72,993,774-73,153,979
LCR-B_cen	121.0 kb	Full 100%	N/A	7:73,153,980-73,275,011
LCR-C_mid	64.0 kb	Full 100%	N/A	7:73,295,064-73,359,055
7q11.23_recurrent_(Williams-Beuren_syndrome)_region_(includes_ELN)	1.4 Mb	Partial 61.3%	N/A	7:73,330,452-74,728,172

ClinGen Dosage Sensitivity Regions

Region ID	Size	Overlap	Type	Dosage Sensitivity	Position
7:73330452-74728172	1.4 Mb	Partial 61.3%	N/A	HI: SUFFICIENT_EVIDENCE TS: SUFFICIENT_EVIDENCE	7:73,330,452-74,728,172

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