rs746797445

Variant names:

• chr7-15686056-C-G
• rs746797445
• NM_005924.5:c.347G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-15686056-C-G
• chr7-15686056-C-T
• chr7-15686056-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005924.5(MEOX2):​c.347G>C​(p.Gly116Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,601,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G116E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MEOX2 NM_005924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17462656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX2	NM_005924.5	MANE Select	c.347G>C	p.Gly116Ala	missense	Exon 1 of 3	NP_005915.2	P50222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX2	ENST00000262041.6	TSL:1 MANE Select	c.347G>C	p.Gly116Ala	missense	Exon 1 of 3	ENSP00000262041.5	P50222
	MEOX2	ENST00000904167.1		c.347G>C	p.Gly116Ala	missense	Exon 1 of 4	ENSP00000574226.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152060 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000886 AC: 2 AN: 225790 AF XY: 0.00000808

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1449458 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 720916

African (AFR) AF: 0.0000603 AC: 2 AN: 33144

American (AMR) AF: 0.00 AC: 0 AN: 43576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39116

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108634

Other (OTH) AF: 0.00 AC: 0 AN: 59992

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152060 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.72	N
REVEL	Uncertain	0.33
Sift	Benign	0.092	T
Sift4G	Benign	0.28	T
Polyphen		0.18	B
Vest4		0.17
MutPred		0.19		Loss of catalytic residue at P112 (P = 0.1103)
MVP		0.77
MPC		0.21
ClinPred		0.43	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.21
Mutation Taster		=88/12	polymorphism

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: rs746797445; hg19: chr7-15725681;