ENST00000560219.2:c.31-1983T>C

Variant names:

• chr15-89776082-T-C
• rs12913572
• ENST00000560219.2:c.31-1983T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000560219.2(MESP2):​c.31-1983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,048 control chromosomes in the GnomAD database, including 8,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8517 hom., cov: 32)
• Consequence: MESP2 ENST00000560219.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-89776082-T-C is Benign according to our data. Variant chr15-89776082-T-C is described in ClinVar as Benign. ClinVar VariationId is 1224835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000560219.2. 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.-276T>C		upstream_gene	N/A	NP_001035047.1	Q0VG99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP2	ENST00000560219.2	TSL:1	c.31-1983T>C		intron	N/A	ENSP00000452998.1	H0YKZ5
	MESP2	ENST00000558723.1	TSL:3	n.39-1983T>C		intron	N/A
	MESP2	ENST00000341735.5	TSL:1 MANE Select	c.-276T>C		upstream_gene	N/A	ENSP00000342392.3	Q0VG99

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49974 AN: 151930 Hom.: 8514 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.329 AC: 50016 AN: 152048 Hom.: 8517 Cov.: 32 AF XY: 0.322 AC XY: 23923 AN XY: 74352

African (AFR) AF: 0.402 AC: 16683 AN: 41472

American (AMR) AF: 0.266 AC: 4065 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.179 AC: 925 AN: 5164

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2378 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22222 AN: 67942

Other (OTH) AF: 0.316 AC: 665 AN: 2102

Alfa AF: 0.327 Hom.: 1055

Bravo AF: 0.332

Asia WGS AF: 0.262 AC: 916 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.0030
PromoterAI		0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12913572; hg19: chr15-90319313;