chr21-41396370-C-T

Variant names:

• chr21-41396370-C-T
• rs441437
• NM_002463.2:c.1070+585C>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+585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,190 control chromosomes in the GnomAD database, including 46,613 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 (46613 hom., cov: 33)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX2	NM_002463.2	c.1070+585C>T		intron_variant	Intron 7 of 13	ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8	c.1070+585C>T		intron_variant	Intron 7 of 13	1	NM_002463.2	ENSP00000333657.3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116380 AN: 152072 Hom.: 46608 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.765 AC: 116419 AN: 152190 Hom.: 46613 Cov.: 33 AF XY: 0.766 AC XY: 56990 AN XY: 74408

African (AFR) AF: 0.503 AC: 20861 AN: 41460

American (AMR) AF: 0.795 AC: 12158 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4276 AN: 5178

South Asian (SAS) AF: 0.858 AC: 4144 AN: 4830

European-Finnish (FIN) AF: 0.851 AC: 9030 AN: 10610

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60283 AN: 68024

Other (OTH) AF: 0.784 AC: 1656 AN: 2112

Alfa AF: 0.851 Hom.: 94700

Bravo AF: 0.750

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.36
PhyloP100		-1.0
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: rs441437; hg19: chr21-42768297;