Table 2 Candidate variants in known ASD/NDD genes/regions by variant type

A. SNVs + indels (dominant)

Proband_ID

Sex

Gene

Position (hg19)

Position (hg38)

Inheritance

Variant type

HGVS.c

HGVS.p

Relevant OMIM phenotypes

ACMG

BRK-48–01

M

WDR37

chr10:1,126,397

chr10:1,080,457

De novo

Dmiss

c.377A > T

p.Tyr126Phe

Neurooculocardiogenitourinary syndrome (AD)

LP

BRK-52–01

F

STAG1

chr3:136,192,388

chr3:136,473,546

De novo

Dmiss

c.1118G > A

p.Arg373Gln

Intellectual developmental disorder (AD)

P

BRK-98–01

F

SCN2A

chr2:166,245,634

chr2:165,389,124

De novo

Dmiss

c.5318C > T

p.Ala1773Val

Developmental and epileptic encephalopathy (AD)

P

BRK-78–01

M

KDM5B

chr1:202,746,168

chr1:202,777,040

De novo

Dmiss

c.259A > T

p.Ile87Phe

Intellectual developmental disorder (AR)

LP

BRK-11–01

F

KCNMA1

chr10:78,647,208

chr10:76,887,450

De novo

frameshift

c.3526dupA

p.Met1176fs

Paroxysmal nonkinesigenic dyskinesia with or without generalized epilepsy (AD)

LP

BRK-86–01

M

EIF5A

chr17:7,214,392

chr17:7,311,073

De novo

Dmiss

c.221C > T

p.Pro74Leu

Faundes-Banka syndrome (AD)

LP

BRK-73–01

M

MTOR

chr1:11,217,287

chr1:11,157,230

De novo

Dmiss

c.4391A > G

p.Asp1464Gly

Smith-Kingsmore syndrome (AD)

LP

BRK-77–01

M

GRIN2B

chr12:13,769,471

chr12:13,616,537

De novo

Dmiss

c.1246 T > C

p.Phe416Leu

Intellectual developmental disorder with or without seizures (AD)

LP

sBRK-05–01

M

MYO5A

chr15:52,676,446

chr15:52,384,249

De novo

Dmiss

c.1826G > A

p.Arg609His

Griscelli syndrome, type 1 (AR)

LP

BRK-13–01,

M,

DNM1

chr9:130,982,567

chr9:128,220,288

Paternal

Dmiss

c.796C > T

p.Arg266Cys

Developmental and epileptic encephalopathy (AD)

VUS

BRK-13–04,

M,

BRK-13–05

F

B. SNVs + indels (recessive)

Proband-ID

Sex

Gene

Position (hg19)

Position (hg38)

Inheritance

Variant type

HGVS.c

HGVS.p

Relevant OMIM phenotypes

ACMG

BRK-87–01

M

NBN

chr8:90,983,432

chr8:89,971,204

HOM

Dmiss

c.671G > A

p.Gly224Glu

Nijmegen breakage syndrome (AR)

VUS

BRK-88–01

F

TRAPPC9

chr8:141,370,230

chr8:140,360,131

HOM

Stop gain

c.1708C > T

p.Arg570*

Intellectual developmental disorder (AR)

P/LP

BRK-54–01

F

TSEN2

chr3:12,544,783

chr3:12,503,284

HOM

Dmiss

c.331G > A

p.Ala111Thr

Pontocerebellar hypoplasia type 2B (AR)

VUS

BRK-57–01

F

UBR1

chr15:43,347,084

chr15:43,054,886

HOM

Dmiss

c.1295 T > C

p.Ile432Thr

Johanson-Blizzard syndrome (AR)

VUS

BRK-58–01

M

MED17

chr11:93,523,767

chr11:93,790,601

HOM

Dmiss

c.445A > G

p.Lys149Glu

Microcephaly, postnatal progressive, with seizures and brain atrophy (AR)

VUS

BRK-59–01

M

TIAM1

chr21:32,513,486

chr21:31,141,168

HOM

Dmiss

c.3724G > A

p.Gly1242Arg

Neurodevelopmental disorder with language delay and seizures (AR)

VUS

BRK-74–01

M

CTSA

chr20:44,523,322

chr20:45,894,683

HOM

Dmiss

c.865G > C

p.Gly289Arg

Galactosialidosis (AR)

VUS

ZNF335

chr20:44,578,150

chr20:45,949,511

HOM

Dmiss

c.3727G > T

p.Val1243Leu

Microcephaly (AR)

VUS

C. SNVs + indels (X-linked)

Proband-ID

Sex

Gene

Position (hg19)

Position (hg38)

Inheritance

Variant type

HGVS.c

HGVS.p

Relevant OMIM phenotypes

ACMG

BRK-41–01

M

PTCHD1

chrX:23,353,126

chrX:23,335,009

X-linked

Dmiss

c.134G > A

p.Arg45His

Autism, susceptibility to, X-linked

VUS

BRK-43–01

M

DMD

chrX:32,663,098

chrX:32,644,981

X-linked

Dmiss

c.1132C > G

p.Gln378Glu

Duchenne muscular dystrophy, syndromic ASD

VUS

BRK-56–01

M

SLC9A6

chrX:135,080,654

chrX:135,998,495

X-linked

Dmiss

c.617G > A

p.Arg206Gln

Intellectual developmental disorder, X-linked

VUS

BRK-76–01

M

WNK3

chrX:54,278,075

chrX:54,251,642

X-linked

Dmiss

c.2413G > C

p.Glu805Gln

Intellectual disability

VUS

BRK-96–01

M

WNK3

chrX:54,337,648

chrX:54,311,215

X-linked

Dmiss

c.614A > G

p.Asn205Ser

Intellectual disability

VUS

D. CNVs

Proband_ID

Sex

Gene/s

Genomic disorder/cytoband

Type

Inheritance

Variant type

Size (kb)

Relevant phenotypes

ACMG

BRK-81–01

M

Multiple

22q11.21

CNVs

De novo

Deletion

1400

Autism

P

BRK-65–01

M

Multiple

16p13.3

CNVs

Maternal

Duplication

1700

Autism

VUS

E. TREs

Proband_ID

Sex

Gene

Position (hg19)

Position (hg38)

Type

Inheritance

Variant type

Motif (TREs)

Relevant phenotypes

BRK-51–01

F

SHANK2

chr11:70,749,120–70749713

chr11:70,903,015–70903608

TREs

Dominant

intronic

AAAAT

Autism

BRK-89–01

F

NCOR2

chr12:124,876,767–124,877,620

chr12:124,392,221–124,393,074

TREs

Dominant

intronic

ACAGAGAGACAGGGAGGAG;ACAGGGAGACAGGGAGGAG

-

F. mtDNA

Proband-ID

Sex

Gene

Variant

Proband Heteroplasmy

Maternal Heteroplasmy

Disorder

BRK-16–01

M

MT-TL1

3243A > G

2.1%

Undetectable

MELAS