dbSNP rs370719073: MEOX2:p.His85Tyr (chr7-15686150-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_005924.5(MEOX2):c.253C>T(p.His85Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,568,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H85D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MEOX2
NM_005924.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.91

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=0.2630281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX2	NM_005924.5 link	c.253C>T	p.His85Tyr	missense_variant	Exon 1 of 3	ENST00000262041.6	NP_005915.2	P50222

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEOX2	ENST00000262041.6 link	c.253C>T	p.His85Tyr	missense_variant	Exon 1 of 3	1	NM_005924.5	ENSP00000262041.5		P50222

Frequencies

GnomAD3 genomes

AF:

0.00000754

AC:

AN:

132600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000307

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

GnomAD3 exomes

AF:

0.00000518

AC:

AN:

192878

Hom.:

AF XY:

0.00

AC XY:

AN XY:

103378

show subpopulations

Gnomad AFR exome

AF:

0.0000889

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

6.97e-7

AC:

AN:

1435440

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711674

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000754

AC:

AN:

132600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64224

show subpopulations

Gnomad4 AFR

AF:

0.0000307

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000833

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.00099

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

Eigen

Benign

-0.025

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.081

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.29

REVEL

Uncertain

0.34

Sift

Benign

0.23

Sift4G

Benign

0.72

Polyphen

0.072

Vest4

0.57

MVP

0.75

MPC

0.41

ClinPred

0.69

GERP RS

5.3

Varity_R

0.23

gMVP

0.40

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over