chr21-41402614-A-G

Variant names:

• chr21-41402614-A-G
• rs466092
• NM_002463.2:c.1573+486A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002463.2(MX2):​c.1573+486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 161,332 control chromosomes in the GnomAD database, including 47,111 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 (44126 hom., cov: 32)
  • Exomes 𝑓: 0.80 (2985 hom.)
• Consequence: MX2 NM_002463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX2	NM_002463.2	c.1573+486A>G		intron_variant	Intron 11 of 13	ENST00000330714.8	NP_002454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX2	ENST00000330714.8	c.1573+486A>G		intron_variant	Intron 11 of 13	1	NM_002463.2	ENSP00000333657.3

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114979 AN: 152032 Hom.: 44124 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.799 AC: 7332 AN: 9182 Hom.: 2985 Cov.: 0 AF XY: 0.797 AC XY: 3714 AN XY: 4658

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.840

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.756 AC: 115023 AN: 152150 Hom.: 44126 Cov.: 32 AF XY: 0.753 AC XY: 56013 AN XY: 74368

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.752

Alfa AF: 0.812 Hom.: 102670

Bravo AF: 0.748

Asia WGS AF: 0.623 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.3
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

Other links and lift over

dbSNP: rs466092; hg19: chr21-42774541;