rs28546919

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001039958.2(MESP2):c.558G>A(p.Gln186Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 617 hom., cov: 0)

Exomes 𝑓: 0.17 ( 677 hom. )

Failed GnomAD Quality Control

Consequence

MESP2
NM_001039958.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.36

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-89776915-G-A is Benign according to our data. Variant chr15-89776915-G-A is described in ClinVar as [Benign]. Clinvar id is 257243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.558G>A	p.Gln186Gln	synonymous_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1	Q0VG99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 link	c.558G>A	p.Gln186Gln	synonymous_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1150G>A		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1150G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

7540

AN:

16080

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.400

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.431

GnomAD2 exomes

AF:

0.0253

AC:

1540

AN:

60828

AF XY:

0.0237

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.000980

Gnomad EAS exome

AF:

0.00295

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00310

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.174

AC:

8831

AN:

50886

Hom.:

677

Cov.:

AF XY:

0.179

AC XY:

4454

AN XY:

24926

show subpopulations

African (AFR)

AF:

0.520

AC:

5081

AN:

9766

American (AMR)

AF:

0.226

AC:

295

AN:

1306

Ashkenazi Jewish (ASJ)

AF:

0.00815

AC:

AN:

368

East Asian (EAS)

AF:

0.00219

AC:

AN:

3194

South Asian (SAS)

AF:

0.422

AC:

1888

AN:

4476

European-Finnish (FIN)

AF:

0.00345

AC:

AN:

1448

Middle Eastern (MID)

AF:

0.400

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.0259

AC:

709

AN:

27354

Other (OTH)

AF:

0.276

AC:

767

AN:

2784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

415

829

1244

1658

2073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.469

AC:

7550

AN:

16108

Hom.:

617

Cov.:

AF XY:

0.469

AC XY:

3596

AN XY:

7668

show subpopulations

African (AFR)

AF:

0.495

AC:

7044

AN:

14244

American (AMR)

AF:

0.379

AC:

240

AN:

634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.447

AC:

136

AN:

304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.400

AC:

AN:

European-Non Finnish (NFE)

AF:

0.106

AC:

AN:

624

Other (OTH)

AF:

0.431

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

328

656

984

1312

1640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.503

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive

Benign:2

Nov 26, 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 provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.44

PhyloP100

-3.4

Mutation Taster

=100/0

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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rs28546919

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