Variant rs118204034 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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=0.39547735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MESP2	NM_001039958.2 linkuse as main transcript	c.241G>A	p.Gly81Arg	missense_variant	1/2	ENST00000341735.5
LOC124903550	XR_007064751.1 linkuse as main transcript	n.12C>T		non_coding_transcript_exon_variant	1/2
LOC124903550	XR_007064752.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MESP2	ENST00000341735.5 linkuse as main transcript	c.241G>A	p.Gly81Arg	missense_variant	1/2	1	NM_001039958.2	P1
MESP2	ENST00000560219.2 linkuse as main transcript	c.31-1467G>A		intron_variant		1
MESP2	ENST00000558723.1 linkuse as main transcript	n.39-1467G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000842

AC:

AN:

118804

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66398

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 SAS exome

AF:

0.0000479

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000296

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.31e-7

Gnomad4 OTH exome

AF:

0.0000349

GnomAD4 genome

Cov.:

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

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

MutationTaster

Benign

1.0

N;N

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

Varity_R

0.20

gMVP

0.38

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