rs118204033

Variant names:

• chr15-89777027-T-C
• rs118204033
• NM_001039958.2:c.670T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001039958.2(MESP2):​c.670T>C​(p.Ser224Pro) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S224F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.363
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024164796).
• BP6: Variant 15-89777027-T-C is Benign according to our data. Variant chr15-89777027-T-C is described in ClinVar as Benign. ClinVar VariationId is 38911.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.670T>C	p.Ser224Pro	missense_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP2	ENST00000341735.5	c.670T>C	p.Ser224Pro	missense_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3
MESP2	ENST00000560219.2	c.31-1038T>C		intron_variant	Intron 2 of 2	1		ENSP00000452998.1
MESP2	ENST00000558723.1	n.39-1038T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive Benign:1

Aug 05, 2010

GeneReviews

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.072
DANN	Benign	0.49
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.13	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.85	N
PhyloP100		-0.36
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.22		Loss of phosphorylation at S224 (P = 0.039);
MVP		0.21
MPC		0.68
ClinPred		0.069	T
GERP RS		-0.36
Varity_R		0.052
gMVP		0.068
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs118204033; hg19: chr15-90320258;