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GeneBe

5-174724776-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002449.5(MSX2):c.117C>T(p.Arg39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,557,378 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

MSX2
NM_002449.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.321
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 -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-174724776-C-T is Benign according to our data. Variant chr5-174724776-C-T is described in ClinVar as [Benign]. Clinvar id is 1651356.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.321 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000886 (135/152330) while in subpopulation AFR AF= 0.00301 (125/41588). AF 95% confidence interval is 0.00258. There are 1 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 136 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSX2NM_002449.5 linkuse as main transcriptc.117C>T p.Arg39= synonymous_variant 1/2 ENST00000239243.7
MSX2NM_001363626.2 linkuse as main transcriptc.117C>T p.Arg39= synonymous_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSX2ENST00000239243.7 linkuse as main transcriptc.117C>T p.Arg39= synonymous_variant 1/21 NM_002449.5 P1
MSX2ENST00000507785.2 linkuse as main transcriptc.117C>T p.Arg39= synonymous_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000893
AC:
136
AN:
152214
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00304
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
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:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000176
AC:
27
AN:
153624
Hom.:
0
AF XY:
0.0000840
AC XY:
7
AN XY:
83368
show subpopulations
Gnomad AFR exome
AF:
0.00335
Gnomad AMR exome
AF:
0.0000800
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:
0.0000854
AC:
120
AN:
1405048
Hom.:
0
Cov.:
36
AF XY:
0.0000721
AC XY:
50
AN XY:
693858
show subpopulations
Gnomad4 AFR exome
AF:
0.00334
Gnomad4 AMR exome
AF:
0.0000551
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.000138
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000886
AC:
135
AN:
152330
Hom.:
1
Cov.:
32
AF XY:
0.000779
AC XY:
58
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00301
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000203
Hom.:
0
Bravo
AF:
0.000873

ClinVar

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

Submissions by phenotype

Cranium bifidum occultum Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 02, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
14
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: rs376630472; hg19: chr5-174151779; API