NM_002449.5:c.80G>A

Variant names:

Variant summary

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

The NM_002449.5(MSX2):c.80G>A(p.Gly27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 1,581,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G27G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MSX2
NM_002449.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.39

Publications

0 publications found

Variant links:

Genes affected

MSX2 (HGNC:7392): (msh homeobox 2) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2. [provided by RefSeq, Jul 2008]

MSX2 Gene-Disease associations (from GenCC):

craniosynostosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet
parietal foramina
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
parietal foramina with cleidocranial dysplasia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
parietal foramina 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MSX2 links:

Genome browser will be placed here

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=0.36493528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002449.5. 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
	MSX2	NM_002449.5	MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 1 of 2	NP_002440.2
	MSX2	NM_001363626.2		c.80G>A	p.Gly27Glu	missense	Exon 1 of 2	NP_001350555.1	D6RIS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSX2	ENST00000239243.7	TSL:1 MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 1 of 2	ENSP00000239243.5	P35548
	MSX2	ENST00000507785.2	TSL:2	c.80G>A	p.Gly27Glu	missense	Exon 1 of 2	ENSP00000427425.1	D6RIS4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.0000107

AC:

AN:

186536

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000207

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:

0.00000280

AC:

AN:

1429284

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

708080

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32832

American (AMR)

AF:

0.00

AC:

AN:

39934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25570

East Asian (EAS)

AF:

0.00

AC:

AN:

38244

South Asian (SAS)

AF:

0.00

AC:

AN:

82366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4900

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096482

Other (OTH)

AF:

0.00

AC:

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000197

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cranium bifidum occultum (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.032

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

0.34

PhyloP100

2.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.10

REVEL

Uncertain

0.29

Sift

Benign

0.27

Sift4G

Benign

1.0

Polyphen

0.90

Vest4

0.30

MutPred

0.28

Gain of solvent accessibility (P = 0.024)

MVP

0.99

MPC

0.50

ClinPred

0.22

GERP RS

3.4

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.075

gMVP

0.49

Mutation Taster

=74/26

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