chr2-1874226-A-G

Variant names:

• chr2-1874226-A-G
• rs4305302
• NM_001303052.2:c.2711+12313T>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.2711+12313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,564 control chromosomes in the GnomAD database, including 9,214 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 0.32 (9214 hom., cov: 31)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.2711+12313T>C		intron_variant	Intron 18 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.2711+12313T>C		intron_variant	Intron 18 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47837 AN: 151446 Hom.: 9201 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.316 AC: 47892 AN: 151564 Hom.: 9214 Cov.: 31 AF XY: 0.315 AC XY: 23347 AN XY: 74044

African (AFR) AF: 0.550 AC: 22679 AN: 41264

American (AMR) AF: 0.207 AC: 3147 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3466

East Asian (EAS) AF: 0.398 AC: 2047 AN: 5146

South Asian (SAS) AF: 0.221 AC: 1059 AN: 4794

European-Finnish (FIN) AF: 0.262 AC: 2741 AN: 10452

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14757 AN: 67900

Other (OTH) AF: 0.270 AC: 567 AN: 2100

Alfa AF: 0.251 Hom.: 16871

Bravo AF: 0.325

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.0
DANN	Benign	0.51
PhyloP100		0.44
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: rs4305302; hg19: chr2-1877998;