Variant 21-41390601-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002463.2(MX2):c.769C>A(p.Gln257Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,614,168 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 8 hom. )

Consequence

MX2
NM_002463.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.129

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011843711).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX2	NM_002463.2 linkuse as main transcript	c.769C>A	p.Gln257Lys	missense_variant	6/14	ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8 linkuse as main transcript	c.769C>A	p.Gln257Lys	missense_variant	6/14	1	NM_002463.2	ENSP00000333657	P1	P20592-1

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000879

AC:

221

AN:

251482

Hom.:

AF XY:

0.000898

AC XY:

122

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000800

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000967

AC:

1414

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000964

AC XY:

701

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000952

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152302

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000815

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.769C>A (p.Q257K) alteration is located in exon 6 (coding exon 5) of the MX2 gene. This alteration results from a C to A substitution at nucleotide position 769, causing the glutamine (Q) at amino acid position 257 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

0.82

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

0.37

Vest4

0.35

MVP

0.87

MPC

0.53

ClinPred

0.079

GERP RS

-7.8

Varity_R

0.66

gMVP

0.41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over