rs113994157

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001039958.2(MESP2):​c.385A>C​(p.Ile129Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MESP2NM_001039958.2 linkc.385A>C p.Ile129Leu missense_variant Exon 1 of 2 ENST00000341735.5 NP_001035047.1 Q0VG99
LOC124903550XR_007064751.1 linkn.-133T>G upstream_gene_variant
LOC124903550XR_007064752.1 linkn.-168T>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MESP2ENST00000341735.5 linkc.385A>C p.Ile129Leu missense_variant Exon 1 of 2 1 NM_001039958.2 ENSP00000342392.3 Q0VG99
MESP2ENST00000560219.2 linkc.31-1323A>C intron_variant Intron 2 of 2 1 ENSP00000452998.1 H0YKZ5
MESP2ENST00000558723.1 linkn.39-1323A>C intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1397730
Hom.:
0
Cov.:
30
AF XY:
0.00000144
AC XY:
1
AN XY:
692968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.77
D
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D
M_CAP
Pathogenic
0.90
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.7
M
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-1.6
N
REVEL
Pathogenic
0.83
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.056
T
Polyphen
0.97
D
Vest4
0.52
MutPred
0.55
Loss of MoRF binding (P = 0.1111);
MVP
0.92
MPC
1.4
ClinPred
0.83
D
GERP RS
3.6
Varity_R
0.79
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90319973; API