2-1801658-G-A

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.3276+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 1,274,804 control chromosomes in the GnomAD database, including 1,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (193 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1718 hom.)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-1801658-G-A is Benign according to our data. Variant chr2-1801658-G-A is described in ClinVar as [Benign]. Clinvar id is 1249518.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYT1L	NM_001303052.2	c.3276+38C>T		intron_variant		ENST00000647738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYT1L	ENST00000647738.2	c.3276+38C>T		intron_variant			NM_001303052.2
	ENST00000638628.1	n.346+1356G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6387 AN: 152146 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.00837

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0594 AC: 13946 AN: 234680 Hom.: 498 AF XY: 0.0612 AC XY: 7771 AN XY: 127036

Gnomad AFR exome AF: 0.00750

Gnomad AMR exome AF: 0.0687

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.0785

Gnomad SAS exome AF: 0.0959

Gnomad FIN exome AF: 0.0773

Gnomad NFE exome AF: 0.0487

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0503 AC: 56420 AN: 1122538 Hom.: 1718 Cov.: 15 AF XY: 0.0522 AC XY: 29933 AN XY: 573768

Gnomad4 AFR exome AF: 0.00887

Gnomad4 AMR exome AF: 0.0694

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.0854

Gnomad4 SAS exome AF: 0.0925

Gnomad4 FIN exome AF: 0.0730

Gnomad4 NFE exome AF: 0.0431

Gnomad4 OTH exome AF: 0.0475

GnomAD4 genome AF: 0.0419 AC: 6385 AN: 152266 Hom.: 193 Cov.: 32 AF XY: 0.0447 AC XY: 3325 AN XY: 74440

Gnomad4 AFR AF: 0.00837

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.0803

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0469 Hom.: 192

Bravo AF: 0.0390

Asia WGS AF: 0.0760 AC: 262 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.0030
Dann	Benign	0.59

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: rs2288178; hg19: chr2-1805430; COSMIC: COSV67705555;