chr2-1839002-T-C

Variant names:

• chr2-1839002-T-C
• rs6728613
• NM_001303052.2:c.3080+147A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001303052.2(MYT1L):​c.3080+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 725,640 control chromosomes in the GnomAD database, including 67,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (20993 hom., cov: 33)
  • Exomes 𝑓: 0.39 (46453 hom.)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.926
• Publications: 14 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

ENSG00000303907 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-1839002-T-C is Benign according to our data. Variant chr2-1839002-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.3080+147A>G		intron_variant	Intron 21 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.3080+147A>G		intron_variant	Intron 21 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74844 AN: 152038 Hom.: 20942 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.389 AC: 223124 AN: 573484 Hom.: 46453 AF XY: 0.385 AC XY: 113400 AN XY: 294248

African (AFR) AF: 0.773 AC: 11198 AN: 14478

American (AMR) AF: 0.346 AC: 6356 AN: 18392

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 5414 AN: 14452

East Asian (EAS) AF: 0.631 AC: 19784 AN: 31334

South Asian (SAS) AF: 0.355 AC: 16111 AN: 45374

European-Finnish (FIN) AF: 0.407 AC: 12384 AN: 30460

Middle Eastern (MID) AF: 0.351 AC: 771 AN: 2196

European-Non Finnish (NFE) AF: 0.358 AC: 138573 AN: 386798

Other (OTH) AF: 0.418 AC: 12533 AN: 30000

GnomAD4 genome AF: 0.493 AC: 74944 AN: 152156 Hom.: 20993 Cov.: 33 AF XY: 0.490 AC XY: 36447 AN XY: 74400

African (AFR) AF: 0.774 AC: 32164 AN: 41536

American (AMR) AF: 0.362 AC: 5542 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3443 AN: 5156

South Asian (SAS) AF: 0.379 AC: 1827 AN: 4820

European-Finnish (FIN) AF: 0.406 AC: 4289 AN: 10576

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24952 AN: 67976

Other (OTH) AF: 0.460 AC: 972 AN: 2114

Alfa AF: 0.401 Hom.: 55600

Bravo AF: 0.506

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.043
DANN	Benign	0.33
PhyloP100		-0.93
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: rs6728613; hg19: chr2-1842774; COSMIC: COSV67702345;