chr2-1792732-T-G

Position:

• chr2-1792732-T-G

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.3277-268A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,524 control chromosomes in the GnomAD database, including 1,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1415 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: 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=-0.91).
• BP6: Variant 2-1792732-T-G is Benign according to our data. Variant chr2-1792732-T-G is described in ClinVar as [Benign]. Clinvar id is 1228336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.3277-268A>C		intron_variant		ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.3277-268A>C		intron_variant			NM_001303052.2	ENSP00000497479

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17904 AN: 151416 Hom.: 1414 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.00505

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.118 AC: 17937 AN: 151524 Hom.: 1415 Cov.: 32 AF XY: 0.117 AC XY: 8649 AN XY: 74050

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0831

Gnomad4 EAS AF: 0.00526

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0801

Gnomad4 OTH AF: 0.115

Alfa AF: 0.109 Hom.: 132

Bravo AF: 0.122

Asia WGS AF: 0.0580 AC: 202 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

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.61

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: rs10168959; hg19: chr2-1796504;