| - GRCh37:
- Chr15:22947075
- GRCh38:
- Chr15:22925993
| CYFIP1 | A328S, A416S, A420S, A450S, A484S | Cognitive impairment, Autism, Atrial septal defect,
Strabismus, Autistic behavior, Delayed speech and language development
| Uncertain significance
(May 16, 2023) | criteria provided, single submitter |
| - GRCh37:
- Chr15:22956561
- GRCh38:
- Chr15:22916507
| CYFIP1 | F169L, F40L, F478L, F566L, F570L, F600L, F634L | Cognitive impairment, Autism, Atrial septal defect,
Strabismus, Autistic behavior, Delayed speech and language development
| Uncertain significance
(May 16, 2023) | criteria provided, single submitter |
| - GRCh37:
- Chr11:31561221
- GRCh38:
- Chr11:31539674
| ELP4 | Y91C | Global developmental delay, Cognitive impairment, Seizure
| Likely pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr11:31653911
- GRCh38:
- Chr11:31632364
| ELP4 | L296I, L297I | Global developmental delay, Cognitive impairment, Seizure
| Likely pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr7:73944168-74138459
| GTF2IRD1, GTF2I | | Cognitive impairment | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr9:131087503
- Chr9:131088063
- GRCh38:
- Chr9:128325224
- Chr9:128325784
| COQ4, COQ4 | G95D, R102H, V70I | Dysmetria, Gait ataxia, Progressive spastic paraparesis,
Cognitive impairment | Pathogenic
(Feb 1, 2020) | criteria provided, single submitter |
| - GRCh37:
- Chr6:42946518
- GRCh38:
- Chr6:42978780
| PEX6 | L124P | Premature ovarian insufficiency, Paroxysmal dystonia, Cerebellar ataxia,
Peripheral neuropathy, Sensorineural hearing impairment, Cognitive impairment
| Pathogenic
(Oct 21, 2019) | no assertion criteria provided |
| - GRCh37:
- Chr2:37349743
- GRCh38:
- Chr2:37122600
| EIF2AK2 | G284S, G325S | Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, Cognitive impairment | Conflicting interpretations of pathogenicity
(Dec 18, 2020) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr4:66948561-69631390
| CENPC, GNRHR, STAP1, TMPRSS11A, TMPRSS11B, TMPRSS11D, TMPRSS11E, TMPRSS11F, UBA6, UGT2B15, UGT2B17, YTHDC1 | | Delayed speech and language development, Cognitive impairment | Uncertain significance
(Apr 26, 2019) | no assertion criteria provided |
| - GRCh37:
- Chr19:15302816
- GRCh38:
- Chr19:15192005
| NOTCH3 | C212R | Migraine, Migraine with aura, Ischemic stroke,
Cognitive impairment, Abnormal cerebral white matter morphology, Depression,
Atypical behavior | Pathogenic | no assertion criteria provided |
| - GRCh37:
- Chr5:71494172
- GRCh38:
- Chr5:72198345
| MAP1B | R1538*, R1664* | not provided, Neurodevelopmental disorder | Pathogenic/Likely pathogenic
(Jul 1, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr5:71492276
- GRCh38:
- Chr5:72196449
| MAP1B | E1032*, E906* | Periventricular nodular heterotopia 9, Autism spectrum disorder, Periventricular nodular heterotopia,
Cognitive impairment, White matter deficit, Hypoplasia of the corpus callosum
| Pathogenic; risk factor
(Jun 29, 2020) | no assertion criteria provided |
| - GRCh37:
- Chr5:71491315
- GRCh38:
- Chr5:72195488
| MAP1B | E586fs, E712fs | Periventricular nodular heterotopia 9, Cognitive impairment, White matter deficit,
Periventricular nodular heterotopia, Hypoplasia of the corpus callosum | Pathogenic; risk factor
(Jun 29, 2020) | no assertion criteria provided |
| - GRCh37:
- Chr3:184075273
- GRCh38:
- Chr3:184357485
| CLCN2 | V259I, V215I | Attention deficit hyperactivity disorder, Periventricular heterotopia, Prominent fingertip pads,
Autistic behavior, Seizure, 2-3 toe syndactyly,
Broad forehead, Clinodactyly of the 5th finger, Cognitive impairment
| Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr1:216258204
- GRCh38:
- Chr1:216084862
| USH2A, USH2A-AS2 | G1668V | High palate, Anxiety, Abnormal upper limb bone morphology,
Brisk reflexes, Distal arthrogryposis, Cognitive impairment,
Abnormality of upper limb joint, Abnormal autonomic nervous system physiology, Abnormality of the upper limb,
Multiple joint contractures, Dislocated radial headChronic pain,
Short stature, not provided, ...see more | Uncertain significance
(Sep 24, 2021) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr17:10293842
- GRCh38:
- Chr17:10390525
| MYHAS, MYH8 | I1915V | Cognitive impairment, Distal arthrogryposis, Abnormality of the upper limb,
Multiple joint contractures, Brisk reflexes, High palate,
Anxiety, Short stature, Chronic pain,
Abnormality of upper limb joint, Abnormal upper limb bone morphologyDislocated radial head,
Abnormal autonomic nervous system physiology, ...see more | Uncertain significance | criteria provided, single submitter |
| - GRCh37:
- Chr12:65110586
- GRCh38:
- Chr12:64716806
| GNS | P532A | Mucopolysaccharidosis, MPS-III-D, Autism, Hallux valgus,
Abnormal aggressive, impulsive or violent behavior, Short toe, Clinodactyly of the 5th toe,
Intellectual disability, profound, Global developmental delay, Mandibular prognathia,
2-3 toe syndactyly, Bulbous noseSeizure,
Aggressive behavior, Profound global developmental delay, Cognitive impairment,
Frontal bossing, Slit-like opening of the exterior auditory meatus, Intellectual disability,
Thick lower lip vermilion, Macroglossia, Widely spaced teeth,
Coarse facial features, Shortening of all phalanges of fingers, ...see more | Uncertain significance
(Oct 17, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr13:102379082-102379083
- GRCh38:
- Chr13:101726732-101726733
| FGF14 | R116fs, R131fs, R163fs, R79fs, R101fs, R100fs, R103fs, R129fs, R168fs | Cryptorchidism, Hypertelorism, Cleft palate,
Bifid uvula, Scoliosis, Patent foramen ovale,
Midface retrusion, Cognitive impairment, Seizure,
Prominent supraorbital ridges, Overfolding of the superior helicesTalipes valgus,
Chronic lung disease, Hypermetropia, Pectus carinatum,
Autism, Disproportionate tall stature, Highly arched eyebrow,
...see more | Likely pathogenic | criteria provided, single submitter |
| - GRCh37:
- Chr12:6458505
- GRCh38:
- Chr12:6349339
| SCNN1A | R476Q, R535Q, R499Q | Bronchiectasis, Combined immunodeficiency, Cognitive impairment,
Chronic diarrhea, Hypothyroidism, Failure to thrive,
not provided | Conflicting interpretations of pathogenicity
(Mar 17, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr5:34937536
- GRCh38:
- Chr5:34937431
| DNAJC21 | R182* | Short stature, Pectus excavatum, Acute myeloid leukemia,
Cognitive impairment, Pancytopenia, Webbed neck,
Abnormality of the tongue, See cases | Pathogenic
(Dec 21, 2022) | criteria provided, single submitter |
| - GRCh37:
- Chr1:165697333-165697334
- GRCh38:
- Chr1:165728096-165728097
| TMCO1 | A153fs, A182fs | Periventricular leukomalacia, Asymmetry of the thorax, Cognitive impairment,
Bifid ribs, Median cleft lip, Cleft palate,
Cleft upper lip, See cases | Likely pathogenic
(Dec 21, 2022) | criteria provided, single submitter |
| - GRCh37:
- Chr17:16875332
- GRCh38:
- Chr17:16972018
| TNFRSF13B | R20C | Cognitive impairment, High forehead, Cafe-au-lait spot,
Frontal bossing, Abnormal basal ganglia MRI signal intensity, Seizure,
Micrognathia, Abnormal basal ganglia morphology, Thoracic scoliosis,
Immunodeficiency, common variable, 2, Immunoglobulin A deficiency 2not provided,
Immunodeficiency, common variable, 2, ...see more | Uncertain significance
(Aug 23, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr1:216420437
- Chr1:216270469
- GRCh38:
- Chr1:216247095
- Chr1:216097127
| USH2A, USH2A | E767fs, L1572F | Usher syndrome type 2A | Pathogenic
(Sep 1, 2016) | no assertion criteria provided |
| - GRCh37:
- Chr6:42933788
- GRCh38:
- Chr6:42966050
| PEX6 | R786W, R698W | not provided, Peroxisome biogenesis disorder 4A (Zellweger), Peroxisome biogenesis disorder 4B,
Peroxisome biogenesis disorder 4A (Zellweger) | Conflicting interpretations of pathogenicity
(Mar 1, 2021) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr2:74154102
- GRCh38:
- Chr2:73926975
| DGUOK, LOC129934096 | P22L | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), Memory impairment, Hypoplasia of the corpus callosum,
Cognitive impairment, Increased CSF lactate, Cerebral atrophy,
Increased serum pyruvate, Migraine with aura, not provided
| Uncertain significance
(Jun 28, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:74173868
- GRCh38:
- Chr2:73946741
| DGUOK | G93E | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), Migraine with aura, Increased CSF lactate,
Increased serum pyruvate, Memory impairment, Cerebral atrophy,
Hypoplasia of the corpus callosum, Cognitive impairment | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- ChrMT:14477
- GRCh38:
- ChrMT:14477
| MT-ND6 | | Cognitive impairment, Muscle spasm, Paresthesia,
Headache, Abnormal brain morphology, Vertigo,
Constriction of peripheral visual field | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- ChrX:56488503-57276424
| SPIN2A, SPIN2B, SPIN3, UBQLN2 | | Cognitive impairment, Abnormal emotion, Global developmental delay,
Delayed speech and language development, Delayed fine motor development, Delayed gross motor development
| Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr8:109990022-110168343
| TRHR | | Cognitive impairment, Brachycephaly, Motor delay,
Abnormality of the eye, Global developmental delay, Intellectual disability, mild,
Generalized hypotonia, Neonatal hypotonia, Delayed speech and language development
| Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr7:90054667-91313448
| CDK14, FZD1 | | Autism, Intellectual disability, moderate, Cognitive impairment,
Global developmental delay, Delayed speech and language development | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr3:184300169-188285627
| FETUB, HRG, TBCCD1, TMEM41A, TRA2B, VPS8, IGF2BP2, KNG1, LPP, MAGEF1, MAP3K13, MASP1, RFC4, RPL39L, C3orf70, CRYGS, RTP1, RTP2, LIPH, AHSG, BCL6, ADIPOQ, DGKG, DNAJB11, EHHADH, EIF4A2, EPHB3, ETV5, RTP4, SENP2, SNORA63, SNORA81, SST, ST6GAL1 | | Cognitive impairment, Short stature | Pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr22:21081260-21431174
| LZTR1, P2RX6, PI4KA, SERPIND1, THAP7, SLC7A4, SNAP29, AIFM3, CRKL | | Cognitive impairment, Brachycephaly, Motor delay,
Abnormality of the eye, Global developmental delay, Intellectual disability, mild,
Generalized hypotonia, Neonatal hypotonia, Delayed speech and language development
| Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr16:29656684-30197341
| MVP, TAOK2, TBX6, TLCD3B, TMEM219, YPEL3, SEZ6L2, SPN, PAGR1, ZG16, PPP4C, PRRT2, QPRT, ALDOA, ASPHD1, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, GDPD3, HIRIP3, INO80E, KCTD13, KIF22, MAPK3, MAZ | | Cognitive impairment, Brachycephaly, Motor delay,
Abnormality of the eye, Global developmental delay, Intellectual disability, mild,
Generalized hypotonia, Neonatal hypotonia, Delayed speech and language development
| Likely pathogenic
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr10:751998-1748992
| ADARB2, GTPBP4, IDI1, IDI2, LARP4B, WDR37 | | Cognitive impairment, Short stature | Uncertain significance
(Jan 1, 2017) | criteria provided, single submitter |
| - GRCh37:
- Chr20:57466866
- GRCh38:
- Chr20:58891811
| GNAS | Q29* | Cushing syndrome, McCune-Albright syndrome, Pseudohypoparathyroidism type 1B,
Pseudopseudohypoparathyroidism, Progressive osseous heteroplasia, Pituitary adenoma 3, multiple types,
Pseudohypoparathyroidism, Pseudohypoparathyroidism type 1C, Pseudohypoparathyroidism type 1B,
Obesity, HypocalcemiaShort stature,
Round face, Brachydactyly, Cognitive impairment,
Tetany, Subcutaneous nodule, not provided,
...see more | Pathogenic
(Feb 6, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr18:21134854
- GRCh38:
- Chr18:23554890
| NPC1 | P474L | Niemann-Pick disease, type C1, Headache, Cognitive impairment,
Cerebellar ataxia, Cataplexy, Speech apraxia,
Postural instability | Pathogenic
(Sep 5, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr13:103525655-103525656
- GRCh38:
- Chr13:102873305-102873306
| ERCC5, BIVM-ERCC5 | L977fs, L1431fs | Pes cavus, Spastic paraplegia, Pectus excavatum,
Cognitive impairment, Abnormal corpus callosum morphology, Polyneuropathy,
Cerebellar atrophy, Dysarthria | Likely pathogenic
(Jun 15, 2015) | criteria provided, single submitter |
| - GRCh37:
- ChrX:53410167
- GRCh38:
- ChrX:53383246
| SMC1A | Q972R, Q994R | Congenital muscular hypertrophy-cerebral syndrome, Developmental and epileptic encephalopathy, 85, with or without midline brain defects, Pes cavus,
Spastic paraplegia, Pectus excavatum, Cognitive impairment,
Abnormal corpus callosum morphology, Polyneuropathy, Cerebellar atrophy,
Dysarthria | Uncertain significance
(Feb 3, 2022) | criteria provided, multiple submitters, no conflicts |
| | | | Plagiocephaly, Hearing impairment, Cognitive impairment
| Uncertain significance
(Aug 20, 2016) | criteria provided, single submitter |
| - GRCh37:
- Chr10:89685308
- GRCh38:
- Chr10:87925551
| PTEN | Y68C, Y241C | PTEN hamartoma tumor syndrome, not provided, Cowden syndrome 1,
See cases, Global developmental delay, Microcephaly,
Cerebral visual impairment, Infantile spasms, Seizure,
Developmental regression, Cognitive impairmentAutism,
Hereditary cancer-predisposing syndrome, ...see more | Pathogenic
(Apr 11, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr7:21856224
- GRCh38:
- Chr7:21816606
| DNAH11 | R3491H | Periventricular leukomalacia, Median cleft lip, Bifid ribs,
Cleft upper lip, Cognitive impairment, Asymmetry of the thorax,
Cleft palate, not specified, not provided,
Ciliary dyskinesia, Primary ciliary dyskinesia 7 ...see more | Conflicting interpretations of pathogenicity
(Aug 29, 2023) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr5:176662864
- GRCh38:
- Chr5:177235863
| NSD1 | W1280*, W1011*, W989*, W1029*, W1140* | Autism, Cleft palate, Hypertelorism,
Midface retrusion, Chronic lung disease, Overfolding of the superior helices,
Talipes valgus, Bifid uvula, Cognitive impairment,
Highly arched eyebrow, Pectus carinatumSeizure,
Scoliosis, Patent foramen ovale, Prominent supraorbital ridges,
Hypermetropia, Disproportionate tall stature, Cryptorchidism,
Sotos syndrome, See cases, ...see more | Pathogenic
(Dec 21, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr2:191851647
- GRCh38:
- Chr2:190986921
| STAT1 | T385M, T332M, T352M, T354M, T355M, T365M, T375M, T383M, T387M, T397M | Inherited Immunodeficiency Diseases, Bronchiectasis, Cognitive impairment,
Chronic diarrhea, Failure to thrive, Hypothyroidism,
Combined immunodeficiency, Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, Immunodeficiency 31B,
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency, not providedAutoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome,
Chronic oral candidiasis, Severe T-cell immunodeficiency, Delayed speech and language development,
Short stature, Primary hypothyroidism, Hypothyroidism,
Liver abscess, See cases, ...see more | Pathogenic
(Dec 21, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- ChrX:139586488-139586489
- GRCh38:
- ChrX:140504323-140504324
| SOX3 | | Pectus excavatum, Abnormality of the tongue, Pancytopenia,
Short stature, Webbed neck, Cognitive impairment,
Acute myeloid leukemia, Abnormal sternum morphology, Bilateral cleft palate,
Autism, Severely reduced visual acuityDelayed speech and language development,
Sensorineural hearing impairment, Rib fusion, Cleft palate,
Relative macrocephaly, Renal agenesis, Unilateral renal agenesis,
Scoliosis, Hemivertebrae, Bilateral cleft lip,
Strabismus, Global developmental delay, Bilateral cleft lip and palate,
Cryptorchidism, Pulmonic stenosis, not provided,
Intellectual disability, X-linked, with panhypopituitarism, ...see more | Conflicting interpretations of pathogenicity
(Aug 5, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr17:7577539
- GRCh38:
- Chr17:7674221
| TP53 | R248W, R116W, R209W, R89W | Li-Fraumeni syndrome | Pathogenic
(Aug 28, 2019) | reviewed by expert panel
FDA Recognized Database |
| - GRCh37:
- Chr2:203379626
- GRCh38:
- Chr2:202514903
| BMPR2 | G182D | Primary pulmonary hypertension, Cognitive impairment, Abnormal basal ganglia MRI signal intensity,
High forehead, Cafe-au-lait spot, Frontal bossing,
Micrognathia, Seizure, Thoracic scoliosis,
Abnormal basal ganglia morphology, not providedPulmonary hypertension, primary, 1,
...see more | Conflicting interpretations of pathogenicity
(Sep 14, 2022) | criteria provided, conflicting interpretations |
| - GRCh37:
- Chr10:124266333
- GRCh38:
- Chr10:122506817
| HTRA1 | R302* | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, not provided | Pathogenic/Likely pathogenic
(Sep 19, 2022) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr18:21118528
- GRCh38:
- Chr18:23538564
| NPC1 | P1007A | not provided, Niemann-Pick disease, type C, Niemann-Pick disease, type C1,
Inborn genetic diseases, Postural instability, Headache,
Cataplexy, Speech apraxia, Cognitive impairment,
Cerebellar ataxia | Pathogenic
(Jul 24, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr1:216420437
- GRCh38:
- Chr1:216247095
| USH2A | E767fs | Rare genetic deafness, Usher syndrome, USH2A-Related Disorders,
Distal arthrogryposis, Abnormality of upper limb joint, Brisk reflexes,
High palate, Abnormal upper limb bone morphology, Abnormality of the upper limb,
Multiple joint contractures, Abnormal autonomic nervous system physiologyShort stature,
Cognitive impairment, Chronic pain, Anxiety,
Dislocated radial head, Retinal dystrophy, Usher syndrome type 2A,
Retinitis pigmentosa 39, not specified, not provided,
Retinitis pigmentosa, Retinitis pigmentosa 39, USH2A-related condition,
Usher syndrome type 2A, Usher syndrome, Inborn genetic diseases,
...see more | Pathogenic
(Aug 22, 2023) | criteria provided, multiple submitters, no conflicts |
| - GRCh37:
- Chr1:97915614
- GRCh38:
- Chr1:97450058
| DPYD | | fluorouracil response - Other, tegafur response - Toxicity, fluorouracil response - Toxicity,
capecitabine response - Toxicity | drug response
(May 24, 2021) | reviewed by expert panel |