chr5-174724776-C-T
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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 GnomAd4 at 135 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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GnomAD4 genome AF: 0.000886 AC: 135AN: 152330Hom.: 1 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74492
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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