chr2-2043625-A-G

Variant names:

• chr2-2043625-A-G
• rs6759709
• NM_001303052.2:c.-158+10353T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303052.2(MYT1L):​c.-158+10353T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,838 control chromosomes in the GnomAD database, including 5,994 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5994 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.-158+10353T>C		intron_variant	Intron 4 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.-158+10353T>C		intron_variant	Intron 4 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41476 AN: 151720 Hom.: 5981 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.241

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41522 AN: 151838 Hom.: 5994 Cov.: 32 AF XY: 0.269 AC XY: 19983 AN XY: 74198

African (AFR) AF: 0.356 AC: 14735 AN: 41388

American (AMR) AF: 0.184 AC: 2804 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.156 AC: 799 AN: 5138

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4802

European-Finnish (FIN) AF: 0.260 AC: 2745 AN: 10560

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17720 AN: 67928

Other (OTH) AF: 0.240 AC: 505 AN: 2108

Alfa AF: 0.245 Hom.: 5623

Bravo AF: 0.274

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.56
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6759709; hg19: chr2-2047397;