rs113994156

Variant names:

• chr15-89776628-A-G
• rs113994156
• NM_001039958.2:c.271A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001039958.2(MESP2):​c.271A>G​(p.Lys91Glu) 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 not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.40
• Publications: 1 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: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	NM_001039958.2	MANE Select	c.271A>G	p.Lys91Glu	missense	Exon 1 of 2	NP_001035047.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	ENST00000341735.5	TSL:1 MANE Select	c.271A>G	p.Lys91Glu	missense	Exon 1 of 2	ENSP00000342392.3
	MESP2	ENST00000560219.2	TSL:1	c.31-1437A>G		intron	N/A	ENSP00000452998.1
	MESP2	ENST00000558723.1	TSL:3	n.39-1437A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1372996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 678086

African (AFR) AF: 0.00 AC: 0 AN: 28452

American (AMR) AF: 0.00 AC: 0 AN: 33884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24116

East Asian (EAS) AF: 0.00 AC: 0 AN: 33696

South Asian (SAS) AF: 0.00 AC: 0 AN: 77190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075460

Other (OTH) AF: 0.00 AC: 0 AN: 57268

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Spondylocostal dysostosis 2, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.94	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Pathogenic	0.79	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Pathogenic	0.97	D
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.61		Loss of methylation at K91 (P = 0.0271)
MVP		0.90
MPC		1.8
ClinPred		0.98	D
GERP RS		3.3
PromoterAI		0.25	Neutral
Varity_R		0.82
gMVP		0.45
Mutation Taster		=15/85	disease causing (ClinVar)

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: rs113994156; hg19: chr15-90319859;