rs2141773765

Variant names:

• chr15-89776368-CGCCTCCTCCGCAGA-C
• rs2141773765
• NM_001039958.2:c.20_33delCGCAGAGCCTCCTC

Your query was ambiguous. Multiple possible variants found:

• chr15-89776368-CGCCTCCTCCGCAGA-C
• chr15-89776368-CGCCTCCTCCGCAGA-CGCCTCCTCCGCAGAGCCTCCTCCGCAGA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_001039958.2(MESP2):​c.20_33delCGCAGAGCCTCCTC​(p.Pro7ArgfsTer355) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,748 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MESP2 NM_001039958.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.24
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903550 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 56 pathogenic variants in the truncated region.
• PP5: Variant 15-89776368-CGCCTCCTCCGCAGA-C is Pathogenic according to our data. Variant chr15-89776368-CGCCTCCTCCGCAGA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1452062.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	NM_001039958.2	MANE Select	c.20_33delCGCAGAGCCTCCTC	p.Pro7ArgfsTer355	frameshift	Exon 1 of 2	NP_001035047.1	Q0VG99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	ENST00000341735.5	TSL:1 MANE Select	c.20_33delCGCAGAGCCTCCTC	p.Pro7ArgfsTer355	frameshift	Exon 1 of 2	ENSP00000342392.3	Q0VG99
	MESP2	ENST00000560219.2	TSL:1	c.31-1688_31-1675delCGCAGAGCCTCCTC		intron	N/A	ENSP00000452998.1	H0YKZ5
	MESP2	ENST00000558723.1	TSL:3	n.39-1688_39-1675delCGCAGAGCCTCCTC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379748 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 681004

African (AFR) AF: 0.00 AC: 0 AN: 30988

American (AMR) AF: 0.00 AC: 0 AN: 35558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 35398

South Asian (SAS) AF: 0.00 AC: 0 AN: 78622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077962

Other (OTH) AF: 0.00 AC: 0 AN: 57632

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2141773765; hg19: chr15-90319599;