rs180992065

chr2-1910225-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.438

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYT1L	NM_001303052.2	c.1817+15T>G		intron_variant		ENST00000647738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYT1L	ENST00000647738.2	c.1817+15T>G		intron_variant			NM_001303052.2

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 752 AN: 151948 Hom.: 1 Cov.: 32

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.: 8 AF XY: 0.00658 AC XY: 880 AN XY: 133692

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.: 45 Cov.: 30 AF XY: 0.00707 AC XY: 5129 AN XY: 725224

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.: 1 Cov.: 32 AF XY: 0.00499 AC XY: 371 AN XY: 74326

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.: 0

Bravo AF: 0.00442

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

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

Other links and lift over

dbSNP: rs180992065; hg19: chr2-1913997;