rs2241685

Variant names:

• chr2-1922221-C-T
• rs2241685
• NM_001303052.2:c.1483+65G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

MYT1L Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 39

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.1483+65G>A		intron_variant	Intron 10 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.1483+65G>A		intron_variant	Intron 10 of 24		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

African (AFR) AF: 0.188 AC: 6053 AN: 32268

American (AMR) AF: 0.117 AC: 4780 AN: 40690

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 1735 AN: 22834

East Asian (EAS) AF: 0.314 AC: 12289 AN: 39172

South Asian (SAS) AF: 0.114 AC: 8851 AN: 77336

European-Finnish (FIN) AF: 0.123 AC: 6277 AN: 51202

Middle Eastern (MID) AF: 0.0961 AC: 500 AN: 5202

European-Non Finnish (NFE) AF: 0.0952 AC: 103197 AN: 1084382

Other (OTH) AF: 0.118 AC: 6861 AN: 58134

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

African (AFR) AF: 0.182 AC: 7573 AN: 41518

American (AMR) AF: 0.112 AC: 1714 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5162

South Asian (SAS) AF: 0.121 AC: 584 AN: 4816

European-Finnish (FIN) AF: 0.120 AC: 1276 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6320 AN: 68004

Other (OTH) AF: 0.110 AC: 233 AN: 2114

Alfa AF: 0.107 Hom.: 4836

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.29
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241685; hg19: chr2-1925993;