chr2-1910225-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001303052.2(MYT1L):c.1817+15T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,609,404 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 45 hom. )

Consequence

MYT1L
NM_001303052.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.438

Publications

1 publications found

Variant links:

Genes affected

MYT1L (HGNC:7623): (myelin transcription factor 1 like) This gene encodes a member of the zinc finger superfamily of transcription factors whose expression, thus far, has been found only in neuronal tissues. The encoded protein belongs to a novel class of cystein-cystein-histidine-cystein zinc finger proteins that function in the developing mammalian central nervous system. Forced expression of this gene in combination with the basic helix-loop-helix transcription factor NeuroD1 and the transcription factors POU class 3 homeobox 2 and achaete-scute family basic helix-loop-helix transcription factor 1 can convert fetal and postnatal human fibroblasts into induced neuronal cells, which are able to generate action potentials. Mutations in this gene have been associated with an autosomal dominant form of cognitive disability and with autism spectrum disorder. Alternative splicing results in multiple variants. [provided by RefSeq, Jul 2017]

MYT1L Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 39
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

MYT1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-1910225-A-C is Benign according to our data. Variant chr2-1910225-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00495 (752/152066) while in subpopulation NFE AF = 0.00716 (487/67992). AF 95% confidence interval is 0.00664. There are 1 homozygotes in GnomAd4. There are 371 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2 link	c.1817+15T>G		intron_variant	Intron 13 of 24	ENST00000647738.2	NP_001289981.1	Q9UL68-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2 link	c.1817+15T>G		intron_variant	Intron 13 of 24		NM_001303052.2	ENSP00000497479.2		Q9UL68-1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

752

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00706

Gnomad FIN

AF:

0.00756

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00716

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00612

AC:

1504

AN:

245942

AF XY:

0.00658

show subpopulations

Gnomad AFR exome

AF:

0.000782

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.00877

Gnomad OTH exome

AF:

0.00533

GnomAD4 exome

AF:

0.00693

AC:

10101

AN:

1457338

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

5129

AN XY:

725224

show subpopulations

African (AFR)

AF:

0.000928

AC:

AN:

33422

American (AMR)

AF:

0.00226

AC:

101

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00756

AC:

651

AN:

86152

European-Finnish (FIN)

AF:

0.00740

AC:

382

AN:

51632

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00766

AC:

8501

AN:

1109642

Other (OTH)

AF:

0.00616

AC:

371

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

521

1043

1564

2086

2607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00495

AC:

752

AN:

152066

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

371

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

41468

American (AMR)

AF:

0.00569

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00707

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00756

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00716

AC:

487

AN:

67992

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00499

Hom.:

Bravo

AF:

0.00442

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 22, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.36

(source)

DANN

Benign

0.31

PhyloP100

-0.44

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over