Genetic Variant MX2:c.-71-2682C>T (chr21-41374154-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002463.2(MX2):c.-71-2682C>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 152,258 control chromosomes in the GnomAD database, including 21,897 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 ( 21890 hom., cov: 33)

Exomes 𝑓: 0.54 ( 7 hom. )

Consequence

MX2
NM_002463.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0460

Publications

46 publications found

Variant links:

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)

MX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX2	NM_002463.2 link	c.-71-2682C>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 link	c.-71-2682C>T		intron_variant	Intron 1 of 13	1	NM_002463.2	ENSP00000333657.3

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74873

AN:

152088

Hom.:

21886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.495

GnomAD4 exome

AF:

0.538

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.492

AC:

74877

AN:

152206

Hom.:

21890

Cov.:

AF XY:

0.500

AC XY:

37213

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.158

AC:

6566

AN:

41538

American (AMR)

AF:

0.652

AC:

9978

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1843

AN:

3472

East Asian (EAS)

AF:

0.794

AC:

4105

AN:

5172

South Asian (SAS)

AF:

0.597

AC:

2879

AN:

4824

European-Finnish (FIN)

AF:

0.627

AC:

6645

AN:

10592

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41161

AN:

67982

Other (OTH)

AF:

0.493

AC:

1042

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1667

3333

5000

6666

8333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.577

Hom.:

114582

Bravo

AF:

0.483

Asia WGS

AF:

0.643

AC:

2235

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

(source)

DANN

Benign

0.75

PhyloP100

-0.046

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over