15-89776554-C-G

Position:

chr15-89776554-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039958.2(MESP2):c.197C>G(p.Ala66Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00567 in 1,532,208 control chromosomes in the GnomAD database, including 391 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 213 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 178 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017988086).

BP6

Variant 15-89776554-C-G is Benign according to our data. Variant chr15-89776554-C-G is described in ClinVar as [Benign]. Clinvar id is 38906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89776554-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP2	NM_001039958.2 linkuse as main transcript	c.197C>G	p.Ala66Gly	missense_variant	1/2	ENST00000341735.5	NP_001035047.1	Q0VG99
LOC124903550	XR_007064751.1 linkuse as main transcript	n.56G>C		non_coding_transcript_exon_variant	1/2
LOC124903550	XR_007064752.1 linkuse as main transcript	n.21G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 linkuse as main transcript	c.197C>G	p.Ala66Gly	missense_variant	1/2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 linkuse as main transcript	c.31-1511C>G		intron_variant		1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 linkuse as main transcript	n.39-1511C>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4339

AN:

152260

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0981

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00576

AC:

727

AN:

126298

Hom.:

AF XY:

0.00439

AC XY:

305

AN XY:

69526

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.000762

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000746

Gnomad OTH exome

AF:

0.00256

GnomAD4 exome

AF:

0.00315

AC:

4340

AN:

1379832

Hom.:

178

Cov.:

AF XY:

0.00273

AC XY:

1859

AN XY:

680776

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00628

Gnomad4 ASJ exome

AF:

0.000681

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000345

Gnomad4 OTH exome

AF:

0.00774

GnomAD4 genome

AF:

0.0285

AC:

4346

AN:

152376

Hom.:

213

Cov.:

AF XY:

0.0270

AC XY:

2010

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0980

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.0337

ESP6500AA

AF:

0.0684

AC:

175

ESP6500EA

AF:

0.000891

AC:

ExAC

AF:

0.00318

AC:

272

Asia WGS

AF:

0.00405

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	curation	GeneReviews	Aug 05, 2010	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.091

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.64

REVEL

Benign

0.12

Sift

Benign

0.068

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.15

MVP

0.50

MPC

0.82

ClinPred

0.024

GERP RS

0.21

Varity_R

0.069

gMVP

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over