rs28462216

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039958.2(MESP2):c.412G>A(p.Val138Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,531,108 control chromosomes in the GnomAD database, including 1,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V138L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.061 ( 900 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 778 hom. )

Consequence

MESP2
NM_001039958.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.612

Publications

5 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016154945).

BP6

Variant 15-89776769-G-A is Benign according to our data. Variant chr15-89776769-G-A is described in ClinVar as [Benign]. Clinvar id is 257239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.412G>A	p.Val138Met	missense_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1	Q0VG99
LOC124903550	XR_007064751.1 link	n.-160C>T		upstream_gene_variant
LOC124903550	XR_007064752.1 link	n.-195C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 link	c.412G>A	p.Val138Met	missense_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1296G>A		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1296G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9282

AN:

152228

Hom.:

901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0377

GnomAD2 exomes

AF:

0.0147

AC:

2266

AN:

154542

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000623

Gnomad OTH exome

AF:

0.00723

GnomAD4 exome

AF:

0.00734

AC:

10124

AN:

1378770

Hom.:

778

Cov.:

AF XY:

0.00737

AC XY:

5020

AN XY:

681270

show subpopulations

African (AFR)

AF:

0.217

AC:

6080

AN:

27964

American (AMR)

AF:

0.0122

AC:

409

AN:

33530

Ashkenazi Jewish (ASJ)

AF:

0.0000922

AC:

AN:

21698

East Asian (EAS)

AF:

0.000197

AC:

AN:

35490

South Asian (SAS)

AF:

0.0280

AC:

2095

AN:

74762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45750

Middle Eastern (MID)

AF:

0.0183

AC:

AN:

5398

European-Non Finnish (NFE)

AF:

0.000467

AC:

503

AN:

1077442

Other (OTH)

AF:

0.0164

AC:

929

AN:

56736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

534

1067

1601

2134

2668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0610

AC:

9296

AN:

152338

Hom.:

900

Cov.:

AF XY:

0.0592

AC XY:

4408

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.209

AC:

8694

AN:

41562

American (AMR)

AF:

0.0201

AC:

307

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0292

AC:

141

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68024

Other (OTH)

AF:

0.0373

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

407

815

1222

1630

2037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0245

Hom.:

133

Bravo

AF:

0.0691

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.185

AC:

771

ESP6500EA

AF:

0.000598

AC:

ExAC

AF:

0.0191

AC:

2281

Asia WGS

AF:

0.0270

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondylocostal dysostosis 2, autosomal recessive

Benign:2

Nov 27, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

0.0014

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.2

PhyloP100

0.61

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.37

REVEL

Uncertain

0.31

Sift

Uncertain

0.014

Sift4G

Benign

0.067

Polyphen

0.99

Vest4

0.094

MPC

0.66

ClinPred

0.026

GERP RS

1.8

PromoterAI

0.27

Neutral

(source)

Varity_R

0.060

gMVP

0.21

Mutation Taster

=99/1

polymorphism (auto)

(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

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rs28462216

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over