15-89776598-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039958.2(MESP2):ā€‹c.241G>Cā€‹(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,524,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4099837).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MESP2NM_001039958.2 linkuse as main transcriptc.241G>C p.Gly81Arg missense_variant 1/2 ENST00000341735.5 NP_001035047.1
LOC124903550XR_007064751.1 linkuse as main transcriptn.12C>G non_coding_transcript_exon_variant 1/2
LOC124903550XR_007064752.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MESP2ENST00000341735.5 linkuse as main transcriptc.241G>C p.Gly81Arg missense_variant 1/21 NM_001039958.2 ENSP00000342392 P1
MESP2ENST00000560219.2 linkuse as main transcriptc.31-1467G>C intron_variant 1 ENSP00000452998
MESP2ENST00000558723.1 linkuse as main transcriptn.39-1467G>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000175
AC:
24
AN:
1372026
Hom.:
0
Cov.:
31
AF XY:
0.0000162
AC XY:
11
AN XY:
677204
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000223
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.62
T
M_CAP
Pathogenic
0.91
D
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.23
Sift
Benign
0.073
T
Sift4G
Uncertain
0.040
D
Polyphen
1.0
D
Vest4
0.30
MutPred
0.30
Gain of helix (P = 0.0022);
MVP
0.77
MPC
1.6
ClinPred
0.63
D
GERP RS
2.6
Varity_R
0.20
gMVP
0.38

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: rs118204034; hg19: chr15-90319829; API