2-1839002-T-C

Position:

• chr2-1839002-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.3080+147A>G		intron_variant		ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.3080+147A>G		intron_variant			NM_001303052.2	ENSP00000497479

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

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.418

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

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.460

Alfa AF: 0.380 Hom.: 23329

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.043
DANN	Benign	0.33

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: rs6728613; hg19: chr2-1842774; COSMIC: COSV67702345;