NM_001039958.2:c.43C>G

Variant names:

• chr15-89776400-C-G
• rs985850317
• NM_001039958.2:c.43C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039958.2(MESP2):​c.43C>G​(p.His15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000979 in 1,532,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.595
• 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: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903550 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15075505).

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.43C>G	p.His15Asp	missense	Exon 1 of 2	NP_001035047.1	Q0VG99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	ENST00000341735.5	TSL:1 MANE Select	c.43C>G	p.His15Asp	missense	Exon 1 of 2	ENSP00000342392.3	Q0VG99
	MESP2	ENST00000560219.2	TSL:1	c.31-1665C>G		intron	N/A	ENSP00000452998.1	H0YKZ5
	MESP2	ENST00000558723.1	TSL:3	n.39-1665C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152256 Hom.: 0 Cov.: 33

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: 0.00000942 AC: 13 AN: 1380352 Hom.: 0 Cov.: 31 AF XY: 0.0000117 AC XY: 8 AN XY: 681280

African (AFR) AF: 0.0000322 AC: 1 AN: 31078

American (AMR) AF: 0.00 AC: 0 AN: 35598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.00 AC: 0 AN: 35452

South Asian (SAS) AF: 0.00 AC: 0 AN: 78694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4074

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1077874

Other (OTH) AF: 0.0000174 AC: 1 AN: 57620

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.59
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.16
Sift	Benign	0.26	T
Sift4G	Benign	0.14	T
Polyphen		0.0050	B
Vest4		0.31
MutPred		0.47		Loss of sheet (P = 0.0457)
MVP		0.57
MPC		0.75
ClinPred		0.060	T
GERP RS		3.2
PromoterAI		0.072	Neutral
Varity_R		0.091
gMVP		0.37
Mutation Taster		=95/5	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: rs985850317; hg19: chr15-90319631;