21-41380411-A-G

Variant names:

• chr21-41380411-A-G
• rs2074560
• NM_002463.2:c.577+260A>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.577+260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,906 control chromosomes in the GnomAD database, including 18,165 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 0.42 (18165 hom., cov: 32)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 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.577+260A>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.577+260A>G		intron	N/A	ENSP00000333657.3
	MX2	ENST00000435611.6	TSL:3	c.577+260A>G		intron	N/A	ENSP00000389256.2
	MX2	ENST00000680862.1		c.577+260A>G		intron	N/A	ENSP00000506423.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63484 AN: 151788 Hom.: 18099 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.419 AC: 63617 AN: 151906 Hom.: 18165 Cov.: 32 AF XY: 0.413 AC XY: 30649 AN XY: 74238

African (AFR) AF: 0.816 AC: 33857 AN: 41480

American (AMR) AF: 0.385 AC: 5876 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1235 AN: 5130

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10550

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16675 AN: 67888

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.296 Hom.: 13543

Bravo AF: 0.447

Asia WGS AF: 0.377 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.31
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2074560; hg19: chr21-42752338;