21-41371400-G-T

Variant names:

• chr21-41371400-G-T
• rs443099
• NM_002463.2:c.-71-5436G>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.-71-5436G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,010 control chromosomes in the GnomAD database, including 21,891 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 0.49 (21891 hom., cov: 32)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX2	NM_002463.2	c.-71-5436G>T		intron_variant	Intron 1 of 13	ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8	c.-71-5436G>T		intron_variant	Intron 1 of 13	1	NM_002463.2	ENSP00000333657.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74811 AN: 151892 Hom.: 21887 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.492 AC: 74815 AN: 152010 Hom.: 21891 Cov.: 32 AF XY: 0.500 AC XY: 37163 AN XY: 74306

African (AFR) AF: 0.157 AC: 6528 AN: 41476

American (AMR) AF: 0.652 AC: 9951 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4145 AN: 5168

South Asian (SAS) AF: 0.596 AC: 2875 AN: 4822

European-Finnish (FIN) AF: 0.627 AC: 6606 AN: 10540

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41169 AN: 67950

Other (OTH) AF: 0.493 AC: 1042 AN: 2112

Alfa AF: 0.541 Hom.: 3100

Bravo AF: 0.484

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		0.70
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: rs443099; hg19: chr21-42743327; COSMIC: COSV58098999; COSMIC: COSV58098999;