rs118204034

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039958.2(MESP2):c.241G>A(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,372,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G81G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

1 publications found

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 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

MESP2 links:

LOC124903550 (HGNC:):

LOC124903550 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.39547735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.241G>A	p.Gly81Arg	missense_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1	Q0VG99
LOC124903550	XR_007064751.1 link	n.12C>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903550	XR_007064752.1 link	n.-24C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 link	c.241G>A	p.Gly81Arg	missense_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1467G>A		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1467G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000842

AC:

AN:

118804

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1372026

Hom.:

Cov.:

AF XY:

0.00000443

AC XY:

AN XY:

677204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28806

American (AMR)

AF:

0.00

AC:

AN:

34532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24476

East Asian (EAS)

AF:

0.0000296

AC:

AN:

33736

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1074558

Other (OTH)

AF:

0.0000349

AC:

AN:

57304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

PhyloP100

1.4

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.23

Sift

Benign

0.073

Sift4G

Uncertain

0.040

Polyphen

1.0

Vest4

0.30

MutPred

0.30

Gain of helix (P = 0.0022);

MVP

0.77

MPC

1.6

ClinPred

0.45

GERP RS

2.6

PromoterAI

0.011

Neutral

(source)

Varity_R

0.20

gMVP

0.38

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs118204034

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over