15-89776368-C-T

Variant names:

• chr15-89776368-C-T
• rs1555439013
• NM_001039958.2:c.11C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039958.2(MESP2):​c.11C>T​(p.Ser4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000725 in 1,379,748 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MESP2 NM_001039958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30621797).

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.11C>T	p.Ser4Leu	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.11C>T	p.Ser4Leu	missense	Exon 1 of 2	ENSP00000342392.3	Q0VG99
	MESP2	ENST00000560219.2	TSL:1	c.31-1697C>T		intron	N/A	ENSP00000452998.1	H0YKZ5
	MESP2	ENST00000558723.1	TSL:3	n.39-1697C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379748 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681004

African (AFR) AF: 0.00 AC: 0 AN: 30988

American (AMR) AF: 0.00 AC: 0 AN: 35558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 35398

South Asian (SAS) AF: 0.00 AC: 0 AN: 78622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077962

Other (OTH) AF: 0.00 AC: 0 AN: 57632

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.70	P
Vest4		0.40
MutPred		0.35		Loss of glycosylation at S4 (P = 0.005)
MVP		0.72
MPC		0.58
ClinPred		0.61	D
GERP RS		3.7
PromoterAI		-0.043	Neutral
Varity_R		0.14
gMVP		0.29
Mutation Taster		=99/1	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: rs1555439013; hg19: chr15-90319599;