rs2048152

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002449.5(MSX2):​c.379+59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,590,150 control chromosomes in the GnomAD database, including 634,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.81 ( 51661 hom., cov: 32)
Exomes 𝑓: 0.90 ( 583103 hom. )

Consequence

MSX2
NM_002449.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.374
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 5-174725097-G-A is Benign according to our data. Variant chr5-174725097-G-A is described in ClinVar as [Benign]. Clinvar id is 1246644.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSX2NM_002449.5 linkuse as main transcriptc.379+59G>A intron_variant ENST00000239243.7
MSX2NM_001363626.2 linkuse as main transcriptc.*3+30G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSX2ENST00000239243.7 linkuse as main transcriptc.379+59G>A intron_variant 1 NM_002449.5 P1
MSX2ENST00000507785.2 linkuse as main transcriptc.*3+30G>A intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.809
AC:
122891
AN:
151910
Hom.:
51651
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.556
Gnomad AMI
AF:
0.808
Gnomad AMR
AF:
0.884
Gnomad ASJ
AF:
0.910
Gnomad EAS
AF:
0.983
Gnomad SAS
AF:
0.905
Gnomad FIN
AF:
0.914
Gnomad MID
AF:
0.889
Gnomad NFE
AF:
0.903
Gnomad OTH
AF:
0.835
GnomAD3 exomes
AF:
0.898
AC:
180895
AN:
201546
Hom.:
81923
AF XY:
0.901
AC XY:
99904
AN XY:
110906
show subpopulations
Gnomad AFR exome
AF:
0.557
Gnomad AMR exome
AF:
0.933
Gnomad ASJ exome
AF:
0.914
Gnomad EAS exome
AF:
0.983
Gnomad SAS exome
AF:
0.912
Gnomad FIN exome
AF:
0.916
Gnomad NFE exome
AF:
0.905
Gnomad OTH exome
AF:
0.900
GnomAD4 exome
AF:
0.899
AC:
1292157
AN:
1438122
Hom.:
583103
Cov.:
41
AF XY:
0.900
AC XY:
642383
AN XY:
713452
show subpopulations
Gnomad4 AFR exome
AF:
0.543
Gnomad4 AMR exome
AF:
0.925
Gnomad4 ASJ exome
AF:
0.912
Gnomad4 EAS exome
AF:
0.976
Gnomad4 SAS exome
AF:
0.912
Gnomad4 FIN exome
AF:
0.912
Gnomad4 NFE exome
AF:
0.904
Gnomad4 OTH exome
AF:
0.888
GnomAD4 genome
AF:
0.809
AC:
122943
AN:
152028
Hom.:
51661
Cov.:
32
AF XY:
0.813
AC XY:
60434
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.556
Gnomad4 AMR
AF:
0.884
Gnomad4 ASJ
AF:
0.910
Gnomad4 EAS
AF:
0.983
Gnomad4 SAS
AF:
0.905
Gnomad4 FIN
AF:
0.914
Gnomad4 NFE
AF:
0.903
Gnomad4 OTH
AF:
0.829
Alfa
AF:
0.865
Hom.:
10587
Bravo
AF:
0.795
Asia WGS
AF:
0.891
AC:
3100
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
7.9
DANN
Benign
0.97

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.

Other links and lift over

dbSNP: rs2048152; hg19: chr5-174152100; API