rs71647806

Variant names:

• chr15-89776730-C-G
• rs71647806
• NM_001039958.2:c.373C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-89776730-C-G
• chr15-89776730-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L125L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:2 U:1
• Conservation: PhyloP100: 1.85
• Publications: 7 publications found

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]

MESP2 Gene-Disease associations (from GenCC):

• spondylocostal dysostosis 2, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903550 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.99

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 Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:2 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive Pathogenic:2

Aug 05, 2010

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Jun 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified Uncertain:1

May 09, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: MESP2 c.373C>G (p.Leu125Val) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.373C>G has been observed in a compound heterozygous individual affected with Spondylocostal Dysostosis 2 (Cornier_2008). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function; however, the data from the luciferase reporter assay does not allow convincing conclusions about the variant effect (Cornier_2008). The following publication have been ascertained in the context of this evaluation (PMID: 18485326). ClinVar contains an entry for this variant (Variation ID: 5185). Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.94	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		1.9
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.96		Gain of methylation at K121 (P = 0.0672);
MVP		0.94
MPC		1.5
ClinPred		0.99	D
GERP RS		2.6
PromoterAI		-0.070	Neutral
Varity_R		0.86
gMVP		0.69
Mutation Taster		=28/72	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71647806; hg19: chr15-90319961;