rs2241685

Positions:

• chr2-1922221-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001303052.2(MYT1L):​c.1483+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,563,390 control chromosomes in the GnomAD database, including 10,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1506 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9314 hom.)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-1922221-C-T is Benign according to our data. Variant chr2-1922221-C-T is described in ClinVar as [Benign]. Clinvar id is 1250002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.1483+65G>A		intron_variant		ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.1483+65G>A		intron_variant			NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19725 AN: 152052 Hom.: 1505 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.107 AC: 150543 AN: 1411220 Hom.: 9314 AF XY: 0.106 AC XY: 73416 AN XY: 695668

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0760

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.130 AC: 19740 AN: 152170 Hom.: 1506 Cov.: 33 AF XY: 0.131 AC XY: 9740 AN XY: 74392

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.110

Alfa AF: 0.102 Hom.: 2145

Bravo AF: 0.133

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.91
CADD	Benign	0.0020
DANN	Benign	0.29

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: rs2241685; hg19: chr2-1925993;