NM_005924.5:c.518-2457T>C

Variant names:

• chr7-15629375-A-G
• rs6958841
• NM_005924.5:c.518-2457T>C

Variant summary

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

The NM_005924.5(MEOX2):​c.518-2457T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,784 control chromosomes in the GnomAD database, including 24,693 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 0.56 (24693 hom., cov: 32)
• Consequence: MEOX2 NM_005924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 3 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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX2	NM_005924.5	c.518-2457T>C		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.518-2457T>C		intron_variant	Intron 1 of 2	1	NM_005924.5	ENSP00000262041.5

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85571 AN: 151666 Hom.: 24683 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.564 AC: 85607 AN: 151784 Hom.: 24693 Cov.: 32 AF XY: 0.558 AC XY: 41367 AN XY: 74180

African (AFR) AF: 0.460 AC: 19034 AN: 41406

American (AMR) AF: 0.569 AC: 8661 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2265 AN: 5132

South Asian (SAS) AF: 0.463 AC: 2234 AN: 4822

European-Finnish (FIN) AF: 0.604 AC: 6373 AN: 10546

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43317 AN: 67882

Other (OTH) AF: 0.562 AC: 1184 AN: 2108

Alfa AF: 0.599 Hom.: 16318

Bravo AF: 0.560

Asia WGS AF: 0.437 AC: 1520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.4
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: rs6958841; hg19: chr7-15669000;