chr15-89776769-G-C

Position:

• chr15-89776769-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039958.2(MESP2):​c.412G>C​(p.Val138Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22572911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP2	NM_001039958.2	c.412G>C	p.Val138Leu	missense_variant	1/2	ENST00000341735.5	NP_001035047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MESP2	ENST00000341735.5	c.412G>C	p.Val138Leu	missense_variant	1/2	1	NM_001039958.2	ENSP00000342392	P1
MESP2	ENST00000560219.2	c.31-1296G>C		intron_variant		1		ENSP00000452998
MESP2	ENST00000558723.1	n.39-1296G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.28
Sift	Benign	0.69	T
Sift4G	Benign	0.68	T
Polyphen		0.0080	B
Vest4		0.22
MutPred		0.43		Gain of disorder (P = 0.05);
MVP		0.75
MPC		0.53
ClinPred		0.035	T
GERP RS		1.8
Varity_R		0.048
gMVP		0.20

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

Other links and lift over

dbSNP: rs28462216; hg19: chr15-90320000;