Variant chr2-1910225-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

MYT1L (HGNC:):

MYT1L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2 linkuse as main transcript	c.1817+15T>G		intron_variant		ENST00000647738.2	NP_001289981.1	Q9UL68-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2 linkuse as main transcript	c.1817+15T>G		intron_variant			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

GnomAD3 exomes

AF:

0.00612

AC:

1504

AN:

245942

Hom.:

AF XY:

0.00658

AC XY:

880

AN XY:

133692

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 SAS exome

AF:

0.00815

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

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00756

Gnomad4 FIN exome

AF:

0.00740

Gnomad4 NFE exome

AF:

0.00766

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00495

AC:

752

AN:

152066

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

371

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00121

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00707

Gnomad4 FIN

AF:

0.00756

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.00332

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

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.36

DANN

Benign

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over