21-41395967-C-T

Variant names:

• chr21-41395967-C-T
• rs442014
• NM_002463.2:c.1070+182C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002463.2(MX2):​c.1070+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,304 control chromosomes in the GnomAD database, including 62,654 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (62654 hom., cov: 34)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 8 publications found

Genes affected

MX2 (HGNC:7533): (MX dynamin like GTPase 2) The protein encoded by this gene has a nuclear and a cytoplasmic form and is a member of both the dynamin family and the family of large GTPases. The nuclear form is localized in a granular pattern in the heterochromatin region beneath the nuclear envelope. A nuclear localization signal (NLS) is present at the amino terminal end of the nuclear form but is lacking in the cytoplasmic form due to use of an alternate translation start codon. This protein is upregulated by interferon-alpha but does not contain the antiviral activity of a similar myxovirus resistance protein 1. [provided by RefSeq, Jul 2008]

MX2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002463.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX2	NM_002463.2	MANE Select	c.1070+182C>T		intron	N/A	NP_002454.1	P20592-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX2	ENST00000330714.8	TSL:1 MANE Select	c.1070+182C>T		intron	N/A	ENSP00000333657.3	P20592-1
	MX2	ENST00000965975.1		c.1118+182C>T		intron	N/A	ENSP00000636034.1
	MX2	ENST00000435611.6	TSL:3	c.1070+182C>T		intron	N/A	ENSP00000389256.2	P20592-1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137935 AN: 152186 Hom.: 62602 Cov.: 34

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.906 AC: 138047 AN: 152304 Hom.: 62654 Cov.: 34 AF XY: 0.906 AC XY: 67440 AN XY: 74452

African (AFR) AF: 0.901 AC: 37461 AN: 41556

American (AMR) AF: 0.949 AC: 14532 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3076 AN: 3472

East Asian (EAS) AF: 0.970 AC: 5033 AN: 5188

South Asian (SAS) AF: 0.872 AC: 4213 AN: 4830

European-Finnish (FIN) AF: 0.873 AC: 9249 AN: 10598

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61479 AN: 68032

Other (OTH) AF: 0.912 AC: 1930 AN: 2116

Alfa AF: 0.903 Hom.: 191656

Bravo AF: 0.913

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-0.49
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: rs442014; hg19: chr21-42767894;