15-89776855-C-G

Position:

• chr15-89776855-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001039958.2(MESP2):​c.498C>G​(p.Pro166Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,459,394 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (35 hom.)
• Consequence: MESP2 NM_001039958.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.524

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 15-89776855-C-G is Benign according to our data. Variant chr15-89776855-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 257240.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 afr. gnomad4 allele frequency = 0.0114 (1739/152316) while in subpopulation AFR AF= 0.0397 (1651/41566). AF 95% confidence interval is 0.0381. There are 33 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MESP2	NM_001039958.2	c.498C>G	p.Pro166Pro	synonymous_variant	1/2	ENST00000341735.5	NP_001035047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MESP2	ENST00000341735.5	c.498C>G	p.Pro166Pro	synonymous_variant	1/2	1	NM_001039958.2	ENSP00000342392.3
MESP2	ENST00000560219.2	c.31-1210C>G		intron_variant		1		ENSP00000452998.1
MESP2	ENST00000558723.1	n.39-1210C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1738 AN: 152200 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00284 AC: 205 AN: 72122 Hom.: 5 AF XY: 0.00220 AC XY: 86 AN XY: 39138

Gnomad AFR exome AF: 0.0496

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000267

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000312

Gnomad OTH exome AF: 0.000468

GnomAD4 exome AF: 0.00114 AC: 1496 AN: 1307078 Hom.: 35 Cov.: 30 AF XY: 0.000986 AC XY: 629 AN XY: 638070

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000170

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000861

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome AF: 0.0114 AC: 1739 AN: 152316 Hom.: 33 Cov.: 33 AF XY: 0.0108 AC XY: 802 AN XY: 74490

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00444

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0000652 Hom.: 0

Bravo AF: 0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.3
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs200336355; hg19: chr15-90320086;