2-1842071-T-C

Variant names:

• chr2-1842071-T-C
• rs4073401
• ENST00000471668.1:c.-1211A>G

Variant summary

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

The ENST00000471668.1(MYT1L):​c.-1211A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,172 control chromosomes in the GnomAD database, including 20,964 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 0.49 (20958 hom., cov: 33)
  • Exomes 𝑓: 0.52 (6 hom.)
• Consequence: MYT1L ENST00000471668.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471668.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	NM_001303052.2	MANE Select	c.2775-1228A>G		intron	N/A	NP_001289981.1	Q9UL68-1
	MYT1L	NM_001329844.2		c.2775-1228A>G		intron	N/A	NP_001316773.1	Q9UL68-1
	MYT1L	NM_001329845.1		c.2775-1228A>G		intron	N/A	NP_001316774.1	Q9UL68-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	ENST00000471668.1	TSL:1	c.-1211A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000497556.1	Q49A74
	MYT1L	ENST00000471668.1	TSL:1	c.-1211A>G		5_prime_UTR	Exon 1 of 3	ENSP00000497556.1	Q49A74
	MYT1L	ENST00000647738.2	MANE Select	c.2775-1228A>G		intron	N/A	ENSP00000497479.2	Q9UL68-1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74770 AN: 152004 Hom.: 20907 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.520 AC: 26 AN: 50 Hom.: 6 Cov.: 0 AF XY: 0.447 AC XY: 17 AN XY: 38

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 18 AN: 36

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.492 AC: 74870 AN: 152122 Hom.: 20958 Cov.: 33 AF XY: 0.490 AC XY: 36405 AN XY: 74354

African (AFR) AF: 0.774 AC: 32134 AN: 41538

American (AMR) AF: 0.362 AC: 5529 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3466

East Asian (EAS) AF: 0.666 AC: 3433 AN: 5152

South Asian (SAS) AF: 0.379 AC: 1821 AN: 4808

European-Finnish (FIN) AF: 0.405 AC: 4282 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24928 AN: 67978

Other (OTH) AF: 0.459 AC: 967 AN: 2108

Alfa AF: 0.406 Hom.: 7379

Bravo AF: 0.505

Asia WGS AF: 0.509 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.38
PhyloP100		-0.20
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4073401;

hg19: chr2-1845843;