rs71647806
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001039958.2(MESP2):c.373C>G(p.Leu125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
MESP2
NM_001039958.2 missense
NM_001039958.2 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
MESP2 (HGNC:29659): (mesoderm posterior bHLH transcription factor 2) This gene encodes a member of the bHLH family of transcription factors and plays a key role in defining the rostrocaudal patterning of somites via interactions with multiple Notch signaling pathways. This gene is expressed in the anterior presomitic mesoderm and is downregulated immediately after the formation of segmented somites. This gene also plays a role in the formation of epithelial somitic mesoderm and cardiac mesoderm. Mutations in the MESP2 gene cause autosomal recessive spondylocostal dystosis 2 (SCD02). [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99
PP5
Variant 15-89776730-C-G is Pathogenic according to our data. Variant chr15-89776730-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 5185.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MESP2 | NM_001039958.2 | c.373C>G | p.Leu125Val | missense_variant | Exon 1 of 2 | ENST00000341735.5 | NP_001035047.1 | |
| LOC124903550 | XR_007064751.1 | n.-121G>C | upstream_gene_variant | |||||
| LOC124903550 | XR_007064752.1 | n.-156G>C | upstream_gene_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MESP2 | ENST00000341735.5 | c.373C>G | p.Leu125Val | missense_variant | Exon 1 of 2 | 1 | NM_001039958.2 | ENSP00000342392.3 | ||
| MESP2 | ENST00000560219.2 | c.31-1335C>G | intron_variant | Intron 2 of 2 | 1 | ENSP00000452998.1 | ||||
| MESP2 | ENST00000558723.1 | n.39-1335C>G | intron_variant | Intron 1 of 1 | 3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spondylocostal dysostosis 2, autosomal recessive Pathogenic:2
Jun 01, 2008
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Aug 05, 2010
GeneReviews
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: curation
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Gain of methylation at K121 (P = 0.0672);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at