Variant 21-41370109-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002463.2(MX2):c.-71-6727C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,188 control chromosomes in the GnomAD database, including 21,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 21157 hom., cov: 33)

Exomes 𝑓: 0.65 ( 14 hom. )

Consequence

MX2
NM_002463.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 21-41370109-C-A is Benign according to our data. Variant chr21-41370109-C-A is described in ClinVar as [Benign]. Clinvar id is 1289877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX2	NM_002463.2 linkuse as main transcript	c.-71-6727C>A		intron_variant		ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8 linkuse as main transcript	c.-71-6727C>A	intron_variant		1	NM_002463.2	ENSP00000333657	P1	P20592-1
MX2	ENST00000435611.6 linkuse as main transcript	c.-72+6720C>A	intron_variant		3		ENSP00000389256	P1	P20592-1
MX2	ENST00000436410.5 linkuse as main transcript	c.-137-2825C>A	intron_variant		3		ENSP00000393975
MX2	ENST00000418103.2 linkuse as main transcript	c.-312C>A	5_prime_UTR_variant, NMD_transcript_variant	1/7	3		ENSP00000410188		P20592-2

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73592

AN:

152018

Hom.:

21150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.648

AC:

AN:

Hom.:

AF XY:

0.650

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.484

AC:

73598

AN:

152134

Hom.:

21157

Cov.:

AF XY:

0.491

AC XY:

36527

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.639

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.584

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.552

Hom.:

5071

Bravo

AF:

0.476

Asia WGS

AF:

0.626

AC:

2173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 32483191) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

DANN

Benign

0.42

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