rs4647952

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002449.5(MSX2):c.-17C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,579,412 control chromosomes in the GnomAD database, including 1,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 80 hom., cov: 32)

Exomes 𝑓: 0.034 ( 933 hom. )

Consequence

MSX2
NM_002449.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.457

Publications

9 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 5-174724643-C-G is Benign according to our data. Variant chr5-174724643-C-G is described in ClinVar as Benign. ClinVar VariationId is 352836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.029 (4420/152160) while in subpopulation NFE AF = 0.0391 (2656/67974). AF 95% confidence interval is 0.0378. There are 80 homozygotes in GnomAd4. There are 2217 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4420 AD gene.

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.-17C>G		5_prime_UTR	Exon 1 of 2	NP_002440.2
	MSX2	NM_001363626.2		c.-17C>G		5_prime_UTR	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.-17C>G		5_prime_UTR	Exon 1 of 2	ENSP00000239243.5	P35548
	MSX2	ENST00000507785.2	TSL:2	c.-17C>G		5_prime_UTR	Exon 1 of 2	ENSP00000427425.1	D6RIS4

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4420

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00587

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.0606

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0614

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0390

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0300

AC:

5776

AN:

192838

AF XY:

0.0291

show subpopulations

Gnomad AFR exome

AF:

0.00491

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.0551

Gnomad EAS exome

AF:

0.0000682

Gnomad FIN exome

AF:

0.0599

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0338

AC:

48229

AN:

1427252

Hom.:

933

Cov.:

AF XY:

0.0332

AC XY:

23488

AN XY:

706880

show subpopulations

African (AFR)

AF:

0.00572

AC:

188

AN:

32860

American (AMR)

AF:

0.0219

AC:

873

AN:

39872

Ashkenazi Jewish (ASJ)

AF:

0.0568

AC:

1448

AN:

25476

East Asian (EAS)

AF:

0.00

AC:

AN:

38234

South Asian (SAS)

AF:

0.0146

AC:

1196

AN:

81966

European-Finnish (FIN)

AF:

0.0605

AC:

3022

AN:

49910

Middle Eastern (MID)

AF:

0.0352

AC:

152

AN:

4324

European-Non Finnish (NFE)

AF:

0.0358

AC:

39208

AN:

1095660

Other (OTH)

AF:

0.0363

AC:

2142

AN:

58950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2448

4896

7343

9791

12239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<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:

0.0290

AC:

4420

AN:

152160

Hom.:

Cov.:

AF XY:

0.0298

AC XY:

2217

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00585

AC:

243

AN:

41544

American (AMR)

AF:

0.0330

AC:

505

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0606

AC:

210

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5154

South Asian (SAS)

AF:

0.0128

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0614

AC:

650

AN:

10582

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0391

AC:

2656

AN:

67974

Other (OTH)

AF:

0.0331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

221

441

662

882

1103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0280

Hom.:

Bravo

AF:

0.0257

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Craniosynostosis 2 (1)

not provided (1)

Parietal foramina 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.46

PromoterAI

-0.28

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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