Variant 7-15686185-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005924.5(MEOX2):c.218A>G(p.His73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MEOX2
NM_005924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

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]

MEOX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22350097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEOX2	NM_005924.5 linkuse as main transcript	c.218A>G	p.His73Arg	missense_variant	1/3	ENST00000262041.6	NP_005915.2	P50222

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEOX2	ENST00000262041.6 linkuse as main transcript	c.218A>G	p.His73Arg	missense_variant	1/3	1	NM_005924.5	ENSP00000262041.5		P50222

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000450

AC:

AN:

222182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

119804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.218A>G (p.H73R) alteration is located in exon 1 (coding exon 1) of the MEOX2 gene. This alteration results from a A to G substitution at nucleotide position 218, causing the histidine (H) at amino acid position 73 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.0051

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.22

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.46

REVEL

Benign

0.26

Sift

Uncertain

0.024

Sift4G

Benign

0.080

Polyphen

0.18

Vest4

0.44

MutPred

0.27

Gain of MoRF binding (P = 0.085);

MVP

0.74

MPC

0.33

ClinPred

0.62

GERP RS

4.3

Varity_R

0.19

gMVP

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over