rs75049807

Variant names:

• chr15-89776888-G-A
• rs75049807
• NM_001039958.2:c.531G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89776888-G-A
• chr15-89776888-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. A177A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.039 (141 hom., cov: 33)
  • Exomes 𝑓: 0.050 (1691 hom.)
• Consequence: MESP2 NM_001039958.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.182
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.531G>A	p.Ala177Ala	synonymous_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP2	ENST00000341735.5	c.531G>A	p.Ala177Ala	synonymous_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3
MESP2	ENST00000560219.2	c.31-1177G>A		intron_variant	Intron 2 of 2	1		ENSP00000452998.1
MESP2	ENST00000558723.1	n.39-1177G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5841 AN: 151638 Hom.: 139 Cov.: 33

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

GnomAD2 exomes AF: 0.0487 AC: 3706 AN: 76110 AF XY: 0.0491

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 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.: 31 AF XY: 0.0497 AC XY: 31487 AN XY: 632938

African (AFR) AF: 0.0172 AC: 474 AN: 27584

American (AMR) AF: 0.0365 AC: 796 AN: 21834

Ashkenazi Jewish (ASJ) AF: 0.0120 AC: 227 AN: 18986

East Asian (EAS) AF: 0.0645 AC: 2171 AN: 33680

South Asian (SAS) AF: 0.0359 AC: 2331 AN: 64862

European-Finnish (FIN) AF: 0.0522 AC: 1810 AN: 34666

Middle Eastern (MID) AF: 0.0233 AC: 95 AN: 4080

European-Non Finnish (NFE) AF: 0.0523 AC: 54333 AN: 1039606

Other (OTH) AF: 0.0415 AC: 2240 AN: 53928

GnomAD4 genome AF: 0.0386 AC: 5851 AN: 151750 Hom.: 141 Cov.: 33 AF XY: 0.0378 AC XY: 2803 AN XY: 74116

African (AFR) AF: 0.0163 AC: 678 AN: 41504

American (AMR) AF: 0.0327 AC: 499 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.0694 AC: 352 AN: 5072

South Asian (SAS) AF: 0.0357 AC: 171 AN: 4794

European-Finnish (FIN) AF: 0.0452 AC: 473 AN: 10474

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0516 AC: 3499 AN: 67858

Other (OTH) AF: 0.0355 AC: 75 AN: 2110

Alfa AF: 0.00345 Hom.: 3

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

Submissions by phenotype

not specified Benign:2

Jun 14, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

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

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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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75049807; hg19: chr15-90320119; COSMIC: COSV59092036;