Genetic Variant MEOX2:p.Asn91Lys (chr7-15686130-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005924.5(MEOX2):c.273C>G(p.Asn91Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,583,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. N91S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

MEOX2
NM_005924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31683886).

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.273C>G	p.Asn91Lys	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.273C>G	p.Asn91Lys	missense	Exon 1 of 3	ENSP00000262041.5	P50222
	MEOX2	ENST00000904167.1		c.273C>G	p.Asn91Lys	missense	Exon 1 of 4	ENSP00000574226.1

Frequencies

GnomAD3 genomes

AF:

0.0000726

AC:

AN:

151426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000267

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000150

AC:

AN:

199666

AF XY:

0.00000933

show subpopulations

Gnomad AFR exome

AF:

0.000169

Gnomad AMR exome

AF:

0.0000353

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:

0.00000349

AC:

AN:

1431870

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709842

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32600

American (AMR)

AF:

0.00

AC:

AN:

39382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25646

East Asian (EAS)

AF:

0.00

AC:

AN:

37818

South Asian (SAS)

AF:

0.00

AC:

AN:

83360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097572

Other (OTH)

AF:

0.00

AC:

AN:

59434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000726

AC:

AN:

151426

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73930

show subpopulations

African (AFR)

AF:

0.000267

AC:

AN:

41192

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5014

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67890

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

M_CAP

Benign

0.047

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.2

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.58

REVEL

Benign

0.21

Sift

Benign

0.14

Sift4G

Benign

0.87

Polyphen

0.014

Vest4

0.62

MutPred

0.38

Gain of methylation at N91 (P = 8e-04)

MVP

0.65

MPC

0.23

ClinPred

0.16

GERP RS

4.5

Varity_R

0.12

gMVP

0.17

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over