21-41402614-A-G

Variant names:

• chr21-41402614-A-G
• rs466092
• NM_002463.2:c.1573+486A>G

Variant summary

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

The NM_002463.2(MX2):​c.1573+486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 161,332 control chromosomes in the GnomAD database, including 47,111 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 0.76 (44126 hom., cov: 32)
  • Exomes 𝑓: 0.80 (2985 hom.)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX2	NM_002463.2	MANE Select	c.1573+486A>G		intron	N/A	NP_002454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX2	ENST00000330714.8	TSL:1 MANE Select	c.1573+486A>G		intron	N/A	ENSP00000333657.3
	MX2	ENST00000481838.5	TSL:1	n.192+486A>G		intron	N/A	ENSP00000505927.1
	MX2	ENST00000435611.6	TSL:3	c.1573+486A>G		intron	N/A	ENSP00000389256.2

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114979 AN: 152032 Hom.: 44124 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.799 AC: 7332 AN: 9182 Hom.: 2985 Cov.: 0 AF XY: 0.797 AC XY: 3714 AN XY: 4658

African (AFR) AF: 0.693 AC: 158 AN: 228

American (AMR) AF: 0.791 AC: 1115 AN: 1410

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 168 AN: 220

East Asian (EAS) AF: 0.547 AC: 152 AN: 278

South Asian (SAS) AF: 0.609 AC: 413 AN: 678

European-Finnish (FIN) AF: 0.871 AC: 155 AN: 178

Middle Eastern (MID) AF: 0.818 AC: 18 AN: 22

European-Non Finnish (NFE) AF: 0.840 AC: 4790 AN: 5704

Other (OTH) AF: 0.782 AC: 363 AN: 464

GnomAD4 genome AF: 0.756 AC: 115023 AN: 152150 Hom.: 44126 Cov.: 32 AF XY: 0.753 AC XY: 56013 AN XY: 74368

African (AFR) AF: 0.645 AC: 26756 AN: 41488

American (AMR) AF: 0.746 AC: 11403 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3079 AN: 5178

South Asian (SAS) AF: 0.616 AC: 2971 AN: 4824

European-Finnish (FIN) AF: 0.842 AC: 8904 AN: 10580

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56606 AN: 68008

Other (OTH) AF: 0.752 AC: 1589 AN: 2114

Alfa AF: 0.806 Hom.: 213242

Bravo AF: 0.748

Asia WGS AF: 0.623 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.3
DANN	Benign	0.33
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs466092; hg19: chr21-42774541;