15-89776855-C-A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_001039958.2(MESP2):​c.498C>A​(p.Pro166Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,459,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P166P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.524

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 15-89776855-C-A is Benign according to our data. Variant chr15-89776855-C-A is described in ClinVar as [Benign]. Clinvar id is 731367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.524 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000348 (53/152318) while in subpopulation EAS AF = 0.00986 (51/5174). AF 95% confidence interval is 0.0077. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MESP2NM_001039958.2 linkc.498C>A p.Pro166Pro synonymous_variant Exon 1 of 2 ENST00000341735.5 NP_001035047.1 Q0VG99
LOC124903550XR_007064751.1 linkn.-246G>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MESP2ENST00000341735.5 linkc.498C>A p.Pro166Pro synonymous_variant Exon 1 of 2 1 NM_001039958.2 ENSP00000342392.3 Q0VG99
MESP2ENST00000560219.2 linkc.31-1210C>A intron_variant Intron 2 of 2 1 ENSP00000452998.1 H0YKZ5
MESP2ENST00000558723.1 linkn.39-1210C>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.000348
AC:
53
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00983
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00121
AC:
87
AN:
72122
AF XY:
0.00125
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0108
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000312
Gnomad OTH exome
AF:
0.000468
GnomAD4 exome
AF:
0.000285
AC:
373
AN:
1307078
Hom.:
0
Cov.:
30
AF XY:
0.000302
AC XY:
193
AN XY:
638070
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26846
American (AMR)
AF:
0.00
AC:
0
AN:
22372
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18848
East Asian (EAS)
AF:
0.0100
AC:
344
AN:
34266
South Asian (SAS)
AF:
0.000139
AC:
9
AN:
64796
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36550
Middle Eastern (MID)
AF:
0.000233
AC:
1
AN:
4284
European-Non Finnish (NFE)
AF:
9.57e-7
AC:
1
AN:
1044984
Other (OTH)
AF:
0.000333
AC:
18
AN:
54132
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
31
62
92
123
154
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152318
Hom.:
0
Cov.:
33
AF XY:
0.000456
AC XY:
34
AN XY:
74492
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41568
American (AMR)
AF:
0.00
AC:
0
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00986
AC:
51
AN:
5174
South Asian (SAS)
AF:
0.000414
AC:
2
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.510
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000555

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive Benign:2
Oct 24, 2019
Natera, Inc.
Significance:Likely 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:1
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.39
CADD
Benign
5.6
DANN
Benign
0.67
PhyloP100
-0.52
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs200336355; hg19: chr15-90320086; COSMIC: COSV59093188; API