15-89776347-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001039958.2(MESP2):c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,530,920 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (8 hom., cov: 33)
  • Exomes 𝑓: 0.011 (98 hom.)
• Consequence: MESP2 NM_001039958.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-89776347-G-A is Benign according to our data. Variant chr15-89776347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00837 (1275/152368) while in subpopulation NFE AF= 0.0128 (868/68034). AF 95% confidence interval is 0.0121. There are 8 homozygotes in gnomad4. There are 608 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MESP2	NM_001039958.2	c.-11G>A		5_prime_UTR_variant	1/2	ENST00000341735.5
LOC124903550	XR_007064751.1	n.263C>T		non_coding_transcript_exon_variant	1/2
LOC124903550	XR_007064752.1	n.228C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MESP2	ENST00000341735.5	c.-11G>A		5_prime_UTR_variant	1/2	1	NM_001039958.2	P1
MESP2	ENST00000560219.2	c.31-1718G>A		intron_variant		1
MESP2	ENST00000558723.1	n.39-1718G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1275 AN: 152250 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00882 AC: 1109 AN: 125702 Hom.: 8 AF XY: 0.00898 AC XY: 621 AN XY: 69152

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.00406

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00225

Gnomad FIN exome AF: 0.00869

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0106 AC: 14629 AN: 1378552 Hom.: 98 Cov.: 30 AF XY: 0.0105 AC XY: 7129 AN XY: 680428

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.0307

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.00243

Gnomad4 FIN exome AF: 0.00817

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.00837 AC: 1275 AN: 152368 Hom.: 8 Cov.: 33 AF XY: 0.00816 AC XY: 608 AN XY: 74514

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00705

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.0137 Hom.: 6

Bravo AF: 0.00787

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Spondylocostal dysostosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.2
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139599055; hg19: chr15-90319578;