Table 2 Intronic pathogenic and likely pathogenic variants detected by GS.
Variant | Variant coordinates | Zygosity | Class | OMIM phenotype | Supporting evidence |
|---|---|---|---|---|---|
NM_000339.2(SLC12A3):c.1670–191C>T | NC_000016.9:g.56917770C>T | Hom | P | Gitelman syndrome, AR (OMIM®: 263800) | PMID: 19668106 and 21051746. Activating cryptic splicing site |
NM_021008.3(DEAF1):c.997+2_997+3del | NC_000011.9:g.680960_680961del | Hom | LP | Dyskinesia, seizures, and intellectual developmental disorder, AR (OMIM®: 617171) | PMID: 26048982 and 24668509. Affecting splicing |
NM_014714.3(IFT140):c.1525–1G>A | NC_000016.9:g.1621536C>T | CH with exonic P sub | LP | Mainzer-Saldino syndrome, AR (OMIM®: 266920) | Affecting canonical splicing site |
NM_005859.4(PURA):c.-12_25del | NC_000005.9:g.139493755_139493791del | Het | LP | Intellectual disability type 31, AD (OMIM®: 616158) | 37 bp deletion affecting the translation initiation codon |
NM_000548.3(TSC2):c.848+281C>T | NC_000016.9:g.2107460C>T | Het | P | Tuberous sclerosis type 2, AD (OMIM®: 613254) | PMID: 10533066 and 11068191. Activating a splice donor site |
NM_001163435.2(TBCK):c.1170+1G>A | NC_000004.11:g.107163626C>T | Hom | LP | Infantile hypotonia with psychomotor retardation and characteristic facies type 3, AR (OMIM®: 616900) | Affecting canonical splicing site, one additional patient in CentoMD® |
NM_000277.1(PAH):c.1066–11G>A | NC_000012.11:g.103237568C>T | Hom | P | Phenylketonuria, AR (OMIM®: 261600) | PMID: 25596310, 25087612, 23500595 and two additional patients in CentoMD® |
NM_020751.2(COG6):c.1167–24A>G | NC_000013.10:g.40273614A>G | Hom | P | Congenital disorder of glycosylation type 3, AR (OMIM®: 614576, OMIM®: 615328) | PMID: 23606727, two additional patients in CentoMD® |
NM_020680.3(SCYL1):c.1386+1G>T | NC_000011.9:g.65302854G>T | Hom | LP | Spinocerebellar ataxia type 21, AR (OMIM®: 616719) | Affecting canonical splicing site |
NM_032801.4(JAM3):c.612+1G>T | NC_000011.9:g.134014890G>T | Hom | P | Hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts, AR (OMIM®: 613730) | Affecting canonical splicing site |
NM_001172086.1(PEX2):c.-17–2A>G | NC_000008.10:g.77896433T>C | Hom | LP | Peroxisome biogenesis disorder type 5A/B, AR (OMIM®: 614866, OMIM®: 614867) | Affecting canonical splicing site |
NM_181789.2(GLDN):c.1028–2A>T | NC_000015.9:g.51693788A>T | Hom | LP | Lethal congenital contracture syndrome type 11, AR (OMIM®: 617194) | Affecting canonical splicing site |
NM_001323544.1(GALNS):c.441–862C>T | NC_000016.9:g.88905035G>A | CH with exonic P sub | LP | Mucopolysaccharidosis IVA, AR (OMIM®: 253000) | Predicted to create a new splicing site. Pathological enzyme levels (galactosamine-6-sulfate sulfatase) |
NM_001127511.2(APC):c.-190G>A | NC_000005.9:g.112043225G>A | Het | P | Familial adenomatous polyposis, AD (OMIM®: 175100) | PMID: 27087319 |
NM_024757.4(EHMT1):c.21+1_21+5del | NC_000009.11:g.140513502_140513506del | Het | LP | Kleefstra syndrome, AD (OMIM®: 610253) | Affecting canonical splicing site, de novo |
NM_000518.4(HBB):c.315+1G>A | NC_000011.9:g.5247806CT | Het | P | Beta-thalassemia, AD (OMIM®: 613985) | Affecting canonical splicing site, PMID: 7151176 and 26193974 |
NM_001029835.2(CCM2):c.535+1G>C | NC_000007.13:g.45104246G>C | Het | LP | Cerebral cavernous malformations type 2, AD (OMIM®: 603284) | Affecting canonical splicing site |
NM_019096.4(GTPBP2):c.1236+1G>A | NC_000006.11:g.43591669C>T | Hom | LP | Jaberi-Elahi syndrome, AR (OMIM®: 617988) | Affecting canonical splicing site |
NM_001171.5(ABCC6):c.2248–2_2248–1del | NC_000016.9:g.16272823_16272824del | CH with 2 exonic VUS sub | P | Pseudoxanthoma elasticum, AR (OMIM®: 264800) | Affecting canonical splicing site, PMID: 15459974 |
NM_000528.3(MAN2B1):c.2356–2A>G | NC_000019.9:g.12760032T>C | Hom | LP | Alpha-mannosidosis, AR (OMIM®: 248500) | Affecting canonical splicing site |
NM_000169.2(GLA):c.1000–72_100–58delins(2400) | NC_000023.10:g.100653145_ 100653159delins(2400) | Hem | P | Fabry disease, XL (OMIM®: 301500) | Pathological lyso-Gb3 biomarker, pathological alpha galactosidase quantification |
NM_007055.3(POLR3A):c.1771–7C>G | NC_000010.10:g.79769440G>C | Hom | P | Hypomyelinating leukodystrophy type 7, AR (OMIM®: 607694) | PMID: 28459997 |
NM_014362.3(HIBCH):c.386–1G>C | NC_000002.11:g.191152365C>G | Het | LP | 3-hydroxyisobutryl-CoA hydrolase deficiency, AR (OMIM®: 250620) | Affecting canonical splicing site |
NM_000521.3(HEXB):c.1082+5G>A | NC_000005.9:g.74011520G>A | Hom | P | Sandhoff disease, AR (OMIM®: 268800) | PMID: 22848519 |
NM_000463.2(UGT1A1):c.-3275T>G | NC_000002.11:g.234665659T>G | Hom | LP | Genetic susceptibility to Gilbert syndrome, AR (OMIM®: 143500) | PMID: 11906189, 29137095, 20057336 |
NM_000463.2(UGT1A1):c.-41_-40dup | NC_000002.11:g.234668893_234668894dup | Hom | P | Genetic susceptibility to Gilbert syndrome, AR (OMIM®: 143500) | PMID: 7565971, 9653159 |
NM_000169.2(GLA):c.762_763ins(300) | NC_000023.10:g.100653811_100653812ins(300) | Het | P | Fabry disease, XL (OMIM®: 301500) | Pathological lyso-Gb3 biomarker |
NM_000124.3(ERCC6):c.543+1G>T | NC_000010.10:g.50738765C>A | Hom | LP | Cockayne syndrome type B, AR (OMIM®: 133540) | Affecting canonical splicing site |
NM_000271.4(NPC1):c.2795+56C>T | NC_000018.9:g.21119719G>A | Hom | LP | Niemann-Pick disease type C1, AR (OMIM®: 257220) | Pathological lyso-SM-509 biomarker |
NM_020451.2(SELENON):c.872+1G>A | NC_000001.10:g.26135642G>T | Hom | LP | Muscular dystrophy rigid spine type 1, AR (OMIM®: 602771) | Affecting canonical splicing site |
NM_000518.4(HBB):c.316–106C>G | NC_000011.9:g.5247062G>C | Het | P | Beta-thalassemia (minor), AD (OMIM®: 613985) | PMID: 19657842, 23425204 |
NM_005629.3(SLC6A8):c.1255–35_1272del | NC_000023.10:g.152959550_152959602del | Het | LP | Cerebral creatine deficiency syndrome type 1, XL (OMIM®: 300352) | Deletion affecting the canonical splicing site |
NM_018010.3(IFT57):c.585+3A>G | NC_000003.11:g.107932775T>C | Hom | LP | Orofaciodigital syndrome type XVIII, AR (OMIM®: 617927) | Predicted to disrupt the highly conserved donor splice site of exon 4 |
NM_022370.3(ROBO3):c.767–1G>A | NC_000011.9:g.124740060G > A | CH with exonic LP del | LP | Gaze palsy, familial horizontal, with progressive scoliosis, type 1, AR (OMIM®: 607313) | Affecting canonical splicing site |
NM_001282281.1(PYCR1):c.621+1G>A | NC_000017.10:g.79892801C>T | CH with exonic P dup | P | Cutis laxa type IIB/IIIB, AR (OMIM®: 612940 / 614438) | Affecting canonical splicing site |
NM_000152.3(GAA):c.-32–13T>G | NC_000017.10:g.78078341T>G | Hom | P | Glycogen storage disease type II, AR (OMIM®: 232300) | PMID: 7881425, co-segregation in affected sibling, alpha-1,4-glucosidase pathologically decreased |
NM_015910.6(WDPCP):c.253+2T>C | NC_000002.11:g.63713674A>G | Het-Het with intronic VUS | LP | Bardet-Biedl syndrome type 15, AR (OMIM®: 615992) | Affecting canonical splicing site |
NM_000117.2(EMD):c.82+1G>A | NC_000023.10:g.153607927G>A | Hem | LP | Emery-Dreifuss muscular dystrophy type 1, XLR (OMIM®: 310300) | Affecting canonical splicing site |
NM_001079537.1(TRAPPC6B):c.149+2T>A | NC_000014.8:g.39628685A>T | Hom | LP | Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, AR (OMIM®: 617862) | Affecting canonical splicing site |
NM_001286704.1(UFM1):c.-273_-271del | NC_000013.10:g.38923902_38923904del | Hom | P | Hypomyelinating leukodystrophy type 14, AR (OMIM®: 617899) | PMID: 28931644, co-segregating in affected sibling |
NM_001849.3(COL6A2):c.1817–3C>G | NC_000021.8:g.47545376C>G | Hom | P | Bethlem myopathy type 1 / Ullrich congenital muscular dystrophy type 1, AR (OMIM®: 158810 / 254090) | PMID: 15689448 and two additional patients in CentoMD® |
