2-1792707-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001303052.2(MYT1L):c.3277-243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 151,854 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (17 hom., cov: 33)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214

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=-0.87).
• BP6: Variant 2-1792707-T-C is Benign according to our data. Variant chr2-1792707-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1981/151854) while in subpopulation NFE AF= 0.0229 (1558/67926). AF 95% confidence interval is 0.022. There are 17 homozygotes in gnomad4. There are 912 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1980 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYT1L	NM_001303052.2	c.3277-243A>G		intron_variant		ENST00000647738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYT1L	ENST00000647738.2	c.3277-243A>G		intron_variant			NM_001303052.2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1980 AN: 151736 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00477

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00611

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00439

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0130 AC: 1981 AN: 151854 Hom.: 17 Cov.: 33 AF XY: 0.0123 AC XY: 912 AN XY: 74206

Gnomad4 AFR AF: 0.00475

Gnomad4 AMR AF: 0.00610

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00439

Gnomad4 NFE AF: 0.0229

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.0164 Hom.: 2

Bravo AF: 0.0129

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.1
Dann	Benign	0.82

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: rs193015196; hg19: chr2-1796479;