chr15-89776930-G-GCAGGGGCAAGGA

Variant names:

• chr15-89776930-G-GCAGGGGCAAGGA
• rs750330966
• NM_001039958.2:c.597_608dupACAGGGGCAAGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001039958.2(MESP2):​c.597_608dupACAGGGGCAAGG​(p.Gly203_Gln204insGlnGlyGlnGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 143,702 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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G203G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MESP2 NM_001039958.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• 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: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	NM_001039958.2	MANE Select	c.597_608dupACAGGGGCAAGG	p.Gly203_Gln204insGlnGlyGlnGly	disruptive_inframe_insertion	Exon 1 of 2	NP_001035047.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	ENST00000341735.5	TSL:1 MANE Select	c.597_608dupACAGGGGCAAGG	p.Gly203_Gln204insGlnGlyGlnGly	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000342392.3
	MESP2	ENST00000560219.2	TSL:1	c.31-1111_31-1100dupACAGGGGCAAGG		intron	N/A	ENSP00000452998.1
	MESP2	ENST00000558723.1	TSL:3	n.39-1111_39-1100dupACAGGGGCAAGG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000598 AC: 3 AN: 50138 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 2 AN: 143702 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 71594

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6868

American (AMR) AF: 0.00 AC: 0 AN: 6324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2800

East Asian (EAS) AF: 0.00 AC: 0 AN: 6576

South Asian (SAS) AF: 0.00 AC: 0 AN: 9192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 438

European-Non Finnish (NFE) AF: 0.0000204 AC: 2 AN: 98242

Other (OTH) AF: 0.00 AC: 0 AN: 6810

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs750330966; hg19: chr15-90320161;