NM_002463.2:c.871+416G>A

Variant names:

• chr21-41391119-G-A
• rs2838034
• NM_002463.2:c.871+416G>A

Variant summary

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

The NM_002463.2(MX2):​c.871+416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,064 control chromosomes in the GnomAD database, including 1,116 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 0.082 (1116 hom., cov: 31)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX2	NM_002463.2	c.871+416G>A		intron_variant	Intron 6 of 13	ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8	c.871+416G>A		intron_variant	Intron 6 of 13	1	NM_002463.2	ENSP00000333657.3

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12485 AN: 151952 Hom.: 1115 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.00689

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0655

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

GnomAD4 genome AF: 0.0822 AC: 12498 AN: 152064 Hom.: 1116 Cov.: 31 AF XY: 0.0808 AC XY: 6006 AN XY: 74334

African (AFR) AF: 0.215 AC: 8902 AN: 41450

American (AMR) AF: 0.0567 AC: 866 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.177 AC: 911 AN: 5158

South Asian (SAS) AF: 0.0542 AC: 261 AN: 4812

European-Finnish (FIN) AF: 0.00689 AC: 73 AN: 10588

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0187 AC: 1268 AN: 67988

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0116 Hom.: 11

Bravo AF: 0.0918

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.57
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2838034; hg19: chr21-42763046;