NM_001039958.2:c.-4_7delGGCCATGGCCC

Variant names:

• chr15-89776349-AGCCCGGCCATG-A
• rs1968360275
• NM_001039958.2:c.-4_7delGGCCATGGCCC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_001039958.2(MESP2):​c.-4_7delGGCCATGGCCC​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MESP2 NM_001039958.2 frameshift, start_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.67

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]

LOC124903550 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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. Fraction of 0.999 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-89776349-AGCCCGGCCATG-A is Pathogenic according to our data. Variant chr15-89776349-AGCCCGGCCATG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3578145.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2	c.-4_7delGGCCATGGCCC	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 2	ENST00000341735.5	NP_001035047.1
MESP2	NM_001039958.2	c.-4_7delGGCCATGGCCC		5_prime_UTR_variant	Exon 1 of 2	ENST00000341735.5	NP_001035047.1
LOC124903550	XR_007064751.1	n.250_260delCATGGCCGGGC		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903550	XR_007064752.1	n.215_225delCATGGCCGGGC		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP2	ENST00000341735.5	c.-4_7delGGCCATGGCCC	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3
MESP2	ENST00000341735	c.-4_7delGGCCATGGCCC		5_prime_UTR_variant	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3
MESP2	ENST00000560219.2	c.31-1711_31-1701delGGCCATGGCCC		intron_variant	Intron 2 of 2	1		ENSP00000452998.1
MESP2	ENST00000558723.1	n.39-1711_39-1701delGGCCATGGCCC		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive Pathogenic:1

Jan 10, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1968360275; hg19: chr15-90319580;