rs75049807

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001039958.2(MESP2):c.531G>A(p.Ala177Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,450,976 control chromosomes in the GnomAD database, including 1,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 141 hom., cov: 33)

Exomes 𝑓: 0.050 ( 1691 hom. )

Consequence

MESP2
NM_001039958.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.182

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 15-89776888-G-A is Benign according to our data. Variant chr15-89776888-G-A is described in ClinVar as [Benign]. Clinvar id is 257241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.182 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.531G>A	p.Ala177Ala	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.531G>A	p.Ala177Ala	synonymous_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1177G>A		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1177G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5841

AN:

151638

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0327

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0692

Gnomad SAS

AF:

0.0358

Gnomad FIN

AF:

0.0452

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0487

AC:

3706

AN:

76110

Hom.:

135

AF XY:

0.0491

AC XY:

2023

AN XY:

41178

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.0796

Gnomad SAS exome

AF:

0.0367

Gnomad FIN exome

AF:

0.0610

Gnomad NFE exome

AF:

0.0550

Gnomad OTH exome

AF:

0.0406

GnomAD4 exome

AF:

0.0496

AC:

64477

AN:

1299226

Hom.:

1691

Cov.:

AF XY:

0.0497

AC XY:

31487

AN XY:

632938

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.0365

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0522

Gnomad4 NFE exome

AF:

0.0523

Gnomad4 OTH exome

AF:

0.0415

GnomAD4 genome

AF:

0.0386

AC:

5851

AN:

151750

Hom.:

141

Cov.:

AF XY:

0.0378

AC XY:

2803

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.0327

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.0694

Gnomad4 SAS

AF:

0.0357

Gnomad4 FIN

AF:

0.0452

Gnomad4 NFE

AF:

0.0516

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.0580

AC:

200

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spondylocostal dysostosis 2, autosomal recessive

Benign:2

Jan 12, 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. -

Nov 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.6

DANN

Benign

0.75

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