Genetic Variant MESP2:p.Glu103Gln (chr15-89776664-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039958.2(MESP2):c.307G>C(p.Glu103Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000975 in 1,538,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Variant links:

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 links:

LOC124903550 (HGNC:):

LOC124903550 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36351928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.307G>C	p.Glu103Gln	missense_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1	Q0VG99
LOC124903550	XR_007064751.1 link	n.-55C>G		upstream_gene_variant
LOC124903550	XR_007064752.1 link	n.-90C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 link	c.307G>C	p.Glu103Gln	missense_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1401G>C		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1401G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

146096

Hom.:

AF XY:

0.0000243

AC XY:

AN XY:

82306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000828

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000312

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000938

AC:

AN:

1386044

Hom.:

Cov.:

AF XY:

0.00000437

AC XY:

AN XY:

686040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000564

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000337

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.40

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.36

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

0.27

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.89

REVEL

Benign

0.29

Sift

Benign

0.22

Sift4G

Benign

0.36

Polyphen

0.15

Vest4

0.12

MVP

0.79

MPC

0.72

ClinPred

0.043

GERP RS

1.6

Varity_R

0.17

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over