Table 4 Pathogenic and likely pathogenic variance in patients with intellectual disability in Peruvian children (n = 38)
From: Identification of intragenic variants in pediatric patients with intellectual disability in Peru
Patient number | Age range (years) | Sex | Gene | Transcript | Position | Amino acid change | ACMG Criteria | ACMG Classification | Type of variant | Condition associated with ID | MIM | Type of inheritance |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
2 | 10–15 | M | GNAS | NM_016592.5 | c.175 C > T | p.Gln59Ter | PVS1, PM2 | Likely pathogenic | Nonsense | Albright hereditary osteodystrophy | 103580 | Autosomal dominant |
4 | 16–20 | M | SCN1A | NM_001165963.4 | c.695delG | - | PVS1, PM2, PP5 | Pathogenic | Frameshift | SCN1A seizure disorders | 619317 607208 604403 | Autosomal dominant |
5 | 0–5 | M | LETM1 | NM_012318.3 | c.1791delinsAA | p.Tyr598fs | PVS1, PM2 | Likely pathogenic | Frameshift | Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction | 604407 | Autosomal recessive |
20 | 10–15 | M | TUBB3 | NM_006086.4 | c.292G > A | p.Gly98Ser | PM1, PP2, PM2, PP3, PP5 | Likely pathogenic | Missense | Cortical dysplasia complex with other brain malformations 1* Fibrosis of extraocular muscles, congenital 3 A | 614039 600638 | Autosomal dominant |
21 | 0–5 | M | BICRA | NM_001394372.1 | c.2753_2754insC | p.Lys918fs | PVS1, PM2 | Likely pathogenic | Frameshift, nonsense | Coffin-Siris Syndrome 12 | 619325 | Autosomal dominant |
25 43 49 63 93 | 0–5 10–15 0–10 0–5 0–5 | F | MECP2 | NM_004992.4 | c.316 C > T£ c.906delC† c.763 C > T†£ c.455 C > G†£ c.880 C > T†£ | p.Arg106Trp p.Ile315fs p.Arg255Ter p.Pro152Arg p.Arg294Ter | PS3, PM2, PM5, PP3, PM1, PP5 PS4, PVS1, PM2, PP5 PS3, PVS1, PM2, PP5 PS4, PP4, PS3, PM6, PM2, PM1, PP5, PM5, PP3 PS4, PS3, PM6, PVS1, PM2, PP5 | Pathogenic Pathogenic Pathogenic Likely pathogenic Pathogenic | Missense Frameshift, nonsense Nonsense Missense Nonsense | MECP2 Disorders | 312750 300496 | X linked dominant |
46 | 5–10 | F | CREBBP | NM_004380.3 | c.6046_6049del | p.Met2016fs | PVS1, PM2 | Likely pathogenic | Frameshift, nonsense | Rubinstein-Taybi Syndrome 1* Menke-Hennekam Syndrome 1 | 180849 618332 | Autosomal dominant |
48 | 5–10 | F | EP300 | NM_001429.4 | c.2959delC | p.Pro987fs | PVS1, PM2 | Likely pathogenic | Frameshift, nonsense | Rubinstein-Taybi Syndrome 2 Menke-Hennekam Syndrome 2 | 613684 618333 | Autosomal dominant |
50 | 0–5 | F | CDKL5 | NM_001323289.2 | c.533G > A | p.Arg178Gln | PS4, PM5, PM2, PM1, PP3, PP5 | Pathogenic | Missense | Developmental and epileptic encephalopathy 2 | 300672 | Autosomal dominant |
53 | 0–5 | F | TAF1 | NM_004606.5 | c.2324G > T | p.Arg775Leu | PM2, PP3, PP2 | Likely Pathogenic | Missense | Intellectual developmental disorder, X-linked, syndromic 33 | 300966 | X linked recessive |
60 | 0–5 | M | ATP7A | NM_000052.7 | c.907 C > T | p.Gln303Ter | PVS1, PM2 | Likely pathogenic | Nonsense | Menkes Disease* Spinal muscular atrophy, distal, X- linked 33 Occipital horn syndrome | 309400 300489 304150 | X linked recessive |
62 | 0–5 | F | CYFIP2 | NM_001037333.3 | c.2423 A > G | p.His808Arg | PM2, PP3, PP2 | Likely pathogenic | Missense | Developmental and epileptic encephalopathy 65 | 618008 | Autosomal dominant |
66 | 0–5 | F | SLC6A8 | NM_005629.4 | c.643G > T | p.Glu215Ter | PVS1, PM2 | Likely pathogenic | Nonsense | Cerebral creatine deficiency syndrome 1 | 300352 | X linked recessive |
73 91 111 | 5–10 0–5 0–5 | F F M | LAMA2 | NM_000426.4 | c.3928G > T c.1798G > T c.7810 C > T/c.9149_9155del | p.Glu1310Ter p.Gly600Ter p.Arg2604Ter/ p.Ser3050fs | PVS1, PM2, PP5 PVS1, PM2, PP5 PVS1, PM2, PP5, PP4/ PVS1, PM2 | Pathogenic Pathogenic Pathogenic/ Likely pathogenic | Nonsense Nonsense Nonsense, frameshift | Muscular dystrophy LAMA2 | 607855 618138 | Autosomal recessive |
74 | 15–20 | M | CBS FBN1 | NM_000071.3 NM_000138.5 | c.836G > T/c.1081G > A c.1900T > C | p.Gly279Val/ p.Ala361Thr p.Ser634Pro | PP3, PM2, PM1, PP2/ PP3, PM2, PS3, PM3 PM2, PP3, PS4, PM1, PP2 | Likely pathogenic/ Likely pathogenic Pathogenic | Missense Missense | Homocystinuria due to cystathionine beta-synthase deficiency Ectopia lentis, familial | 236200 129600 | Autosomal recessive Autosomal dominant |
75 | 10–15 | M | SLC2A1 | NM_006516.4 | c.80G > A | p.Gly27Asp | PM2, PP3, PP2 | Pathogenic | Missense | GLUT1 Deficiency syndrome 1, infantile onset* GLUT1 Deficiency syndrome 2, childhood onset Dystonia 9 Stomatin-deficient cryohydrocytosis with neurologic defects Susceptibility to epilepsy, idiopathic generalized 12 | 606777 612126 601042 608885 614847 | Autosomal dominant |
79 | 0–5 | F | FGFR1 | NM_023110.3 | c.1958 A > G | p.Tyr653Cys | PM1, PP2, PM2, PP3 | Likely pathogenic | Missense | Hartsfield Syndrome* Jackson-Weiss Syndrome Trigonocephaly 1 | 615465 123150 190440 | Autosomal dominant |
81 | 10–15 | M | POLG | NM_002693.3 | c.1760 C > T/c.752 C > T | p.Pro587Leu/ p.Thr251Ile | PS4, PM3, PM2, PP3, PM1/ PS4, PM2, PM3, PM1, PP3 | Pathogenic/ Pathogenic | Missense | Mitochondrial DNA depletion syndrome 4 A Mitochondrial DNA depletion syndrome 4B Mitochondrial recessive ataxia syndrome Progressive external ophthalmoplegia 1 | 203700 613662 607459 258450 | Autosomal recessive |
82 | 10–15 | M | SETD2 | NM_014159.7 | c.19 C > T | p.Gln7Ter | PVS1, PP4 | Likely pathogenic | Nonsense | Intellectual developmental disorder, autosomal dominant 70 Luscan-Lumish Syndrome Rabin-Pappas Syndrome | 620157 616831 620155 | Autosomal dominant |
83 | 0–5 | M | GRIN2B | NM_000834.5 | c.2471T > A | p.Met824Lys | PM1, PP2, PM2, PM5, PP3 | Likely pathogenic | Missense | Intellectual developmental disorder, autosomal dominant 6 | 619370 | Autosomal dominant |
87 | 5–10 | F | NF1 | NM_001042492.3 | c.4284delT | p.Asp1428fs | PVS1, PM2 | Pathogenic | Frameshift, nonsense | Neurofibromatosis 1* Neurofibromatosis, familial spinal Noonan-neurofibromatosis Syndrome Watson Syndrome Juvenile Myelomonocytic Leukemia | 162200 162210 601321 193520 607785 | Autosomal dominant |
90 | 5–10 | F | FGFR2 | NM_000141.5 | c.1694 A > G | p.Glu565Gly | PS4, PP3, PM2, PM5, PP2, PP5 | Pathogenic | Missense | Pfeiffer Syndrome* Other craniosynostosis syndromes | 101600 | Autosomal dominant |
98 | 0–10 | M | OCRL | NM_000276.4 | c.2083 C > T | p.Arg695Ter | PM3, PVS1, PM2, PP5 | Pathogenic | Nonsense | Dent Syndrome 2 Lowe Syndrome | 300555 309000 | X linked recessive |
102 | 5–10 | M | MMACHC | NM_015506.3 | c.394 C > T | p.Arg132Ter | PM3, PS4, PS3, PVS1, PM2, PP5 | Pathogenic | Nonsense | Methylmalonic aciduria and homocystinuria, cblD type | 277410 | Autosomal recessive |
104 | 5–10 | F | MAGEL2 | NM_019066.5 | c.1808 C > G | p.Ser603Ter | PS4, PVS1, PM2, PP5 | Pathogenic | Nonsense | Schaaf-Yang Syndrome | 615547 | Autosomal dominant |
106 | 5–10 | F | MTOR | NM_004958.4 | C.7216G > A | p.Val2406Met | PM2, PP3, PP2 | Pathogenic | Missense | Smith-Kingsmore Syndrome | 616638 | Autosomal dominant |
107 | 0–5 | F | MUT | NM_000255.4 | c.1084- 1_1084delinsTT/ c.785G > A | - / p.Ser262Asn | PVS1, PM2/ PM3, PM2, PP3, PM5 | Likely pathogenic/ Likely pathogenic | Frameshift Missense | Methylmalonic aciduria, mut (0) type | 251000 | Autosomal recessive |
112 115 | 0–5 0–5 | M | STXBP1 | NM_001032221.6 | c.2T > G c.875G > A | p.Met1Arg p.Arg292His | PM2, PVS1, PP5 PM1, PP2, PM2, PM5, PP3, PP5 | Likely pathogenic Pathogenic | Missense | Developmental and epileptic encephalopathy 4 | 612164 | Autosomal dominant |
118 | 5–10 | M | ANKRD11 | NM_013275.6 | c.3562 C > T | p.Arg1188Ter | PS4, PVS1, PM2, PP5 | Pathogenic | Nonsense | KBG Syndrome | 148050 | Autosomal dominant |
121 | 15–20 | F | CA8 | NM_004056.6 | c.823 C > T | p.Arg275Trp | PP3, PM2, PM1 | Likely pathogenic | Missense | Cerebellar ataxia, impaired intellectual development and disequilibrium syndrome | 613227 | Autosomal recessive |
122 | 0–5 | M | MED13L | NM_015335.5 | c.5461 C > T | p.Gln1821Ter | PVS1, PM2 | Likely pathogenic | Nonsense | Impaired intellectual development and distinctive facial features with or without cardiac defects | 616789 | Autosomal dominant |