Variant 15-89776347-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.463

Variant links:

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 links:

LOC124903550 (HGNC:):

LOC124903550 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 8 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1275

AN:

152250

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00898

AC XY:

621

AN XY:

69152

show subpopulations

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.:

Cov.:

AF XY:

0.0105

AC XY:

7129

AN XY:

680428

show subpopulations

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.:

Cov.:

AF XY:

0.00816

AC XY:

608

AN XY:

74514

show subpopulations

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.:

Bravo

AF:

0.00787

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Spondylocostal dysostosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over