chr5-174724776-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
NM_002449.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.321
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
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
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
?
Synonymous conserved (PhyloP=0.321 with no splicing effect.
BS1
?
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
?
High AC in GnomAd at 136 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSX2 | NM_002449.5 | c.117C>T | p.Arg39= | synonymous_variant | 1/2 | ENST00000239243.7 | |
MSX2 | NM_001363626.2 | c.117C>T | p.Arg39= | synonymous_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSX2 | ENST00000239243.7 | c.117C>T | p.Arg39= | synonymous_variant | 1/2 | 1 | NM_002449.5 | P1 | |
MSX2 | ENST00000507785.2 | c.117C>T | p.Arg39= | synonymous_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000893 AC: 136AN: 152214Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000176 AC: 27AN: 153624Hom.: 0 AF XY: 0.0000840 AC XY: 7AN XY: 83368
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GnomAD4 exome AF: 0.0000854 AC: 120AN: 1405048Hom.: 0 Cov.: 36 AF XY: 0.0000721 AC XY: 50AN XY: 693858
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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 submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at