NM_005924.5:c.518-1549C>G

Variant names:

• chr7-15628467-G-C
• rs4436006
• NM_005924.5:c.518-1549C>G

Variant summary

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

The NM_005924.5(MEOX2):​c.518-1549C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,630 control chromosomes in the GnomAD database, including 32,691 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 (32691 hom., cov: 32)
• Consequence: MEOX2 NM_005924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX2	NM_005924.5	c.518-1549C>G		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.518-1549C>G		intron_variant	Intron 1 of 2	1	NM_005924.5	ENSP00000262041.5

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99118 AN: 151514 Hom.: 32660 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.654 AC: 99202 AN: 151630 Hom.: 32691 Cov.: 32 AF XY: 0.651 AC XY: 48239 AN XY: 74102

African (AFR) AF: 0.682 AC: 28182 AN: 41326

American (AMR) AF: 0.683 AC: 10386 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3468

East Asian (EAS) AF: 0.807 AC: 4148 AN: 5138

South Asian (SAS) AF: 0.496 AC: 2393 AN: 4824

European-Finnish (FIN) AF: 0.650 AC: 6848 AN: 10528

Middle Eastern (MID) AF: 0.466 AC: 135 AN: 290

European-Non Finnish (NFE) AF: 0.639 AC: 43367 AN: 67826

Other (OTH) AF: 0.630 AC: 1329 AN: 2110

Alfa AF: 0.557 Hom.: 1726

Bravo AF: 0.666

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		2.1
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: rs4436006; hg19: chr7-15668092;