15-89776082-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903550	XR_007064751.1	n.320+208A>G		intron_variant, non_coding_transcript_variant
LOC124903550	XR_007064752.1	n.493A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MESP2	ENST00000560219.2	c.31-1983T>C		intron_variant		1
MESP2	ENST00000558723.1	n.39-1983T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.316

Alfa AF: 0.327 Hom.: 1055

Bravo AF: 0.332

Asia WGS AF: 0.262 AC: 916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	13
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12913572; hg19: chr15-90319313;