NM_005924.5:c.518-4099C>A

Variant names:

• chr7-15631017-G-T
• rs2237496
• NM_005924.5:c.518-4099C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005924.5(MEOX2):​c.518-4099C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,686 control chromosomes in the GnomAD database, including 32,062 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 0.65 (32062 hom., cov: 31)
• Consequence: MEOX2 NM_005924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 2 publications found

Genes affected

MEOX2 (HGNC:7014): (mesenchyme homeobox 2) This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the regulation of vertebrate limb myogenesis. Mutations in the related mouse protein may be associated with craniofacial and/or skeletal abnormalities, in addition to neurovascular dysfunction observed in Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX2	NM_005924.5	c.518-4099C>A		intron_variant	Intron 1 of 2	ENST00000262041.6	NP_005915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEOX2	ENST00000262041.6	c.518-4099C>A		intron_variant	Intron 1 of 2	1	NM_005924.5	ENSP00000262041.5

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98152 AN: 151570 Hom.: 32039 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.648 AC: 98228 AN: 151686 Hom.: 32062 Cov.: 31 AF XY: 0.645 AC XY: 47786 AN XY: 74098

African (AFR) AF: 0.657 AC: 27228 AN: 41414

American (AMR) AF: 0.680 AC: 10333 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1900 AN: 3458

East Asian (EAS) AF: 0.806 AC: 4140 AN: 5138

South Asian (SAS) AF: 0.496 AC: 2394 AN: 4822

European-Finnish (FIN) AF: 0.654 AC: 6907 AN: 10562

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43372 AN: 67794

Other (OTH) AF: 0.624 AC: 1312 AN: 2102

Alfa AF: 0.618 Hom.: 12844

Bravo AF: 0.657

Asia WGS AF: 0.592 AC: 2056 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.70
PhyloP100		-0.17
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: rs2237496; hg19: chr7-15670642;