2-1801913-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.3173-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 641,098 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (4 hom.)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149

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=-0.87).
• BP6: Variant 2-1801913-T-C is Benign according to our data. Variant chr2-1801913-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00353 (538/152290) while in subpopulation AFR AF= 0.0124 (517/41562). AF 95% confidence interval is 0.0116. There are 3 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 537 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYT1L	NM_001303052.2	c.3173-114A>G		intron_variant		ENST00000647738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYT1L	ENST00000647738.2	c.3173-114A>G		intron_variant			NM_001303052.2
	ENST00000638628.1	n.346+1611T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00353 AC: 537 AN: 152172 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000368 AC: 180 AN: 488808 Hom.: 4 Cov.: 6 AF XY: 0.000336 AC XY: 87 AN XY: 259032

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000146

Gnomad4 FIN exome AF: 0.0000316

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.000746

GnomAD4 genome AF: 0.00353 AC: 538 AN: 152290 Hom.: 3 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74466

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00402

Asia WGS AF: 0.00173 AC: 6 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

Dec 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.5
Dann	Benign	0.47

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: rs116577745; hg19: chr2-1805685;