rs6959221

Variant names:

• chr7-15629358-G-C
• rs6959221
• NM_005924.5:c.518-2440C>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.518-2440C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,692 control chromosomes in the GnomAD database, including 24,473 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 (24473 hom., cov: 32)
• Consequence: MEOX2 NM_005924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX2	NM_005924.5	c.518-2440C>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.518-2440C>G		intron_variant	Intron 1 of 2	1	NM_005924.5	ENSP00000262041.5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85173 AN: 151574 Hom.: 24468 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.562 AC: 85200 AN: 151692 Hom.: 24473 Cov.: 32 AF XY: 0.555 AC XY: 41174 AN XY: 74134

African (AFR) AF: 0.457 AC: 18891 AN: 41364

American (AMR) AF: 0.568 AC: 8641 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1902 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2229 AN: 5140

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4822

European-Finnish (FIN) AF: 0.603 AC: 6354 AN: 10530

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

European-Non Finnish (NFE) AF: 0.636 AC: 43149 AN: 67846

Other (OTH) AF: 0.558 AC: 1175 AN: 2104

Alfa AF: 0.593 Hom.: 3364

Bravo AF: 0.557

Asia WGS AF: 0.432 AC: 1503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.66
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: rs6959221; hg19: chr7-15668983;