rs749710849

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001039958.2(MESP2):c.549_584delGCAGGGGCAGGGGCAGGGGCAAGGGCAGGGGCAAGG(p.Gln184_Gly195del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G183G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0089 ( 2 hom., cov: 0)

Exomes 𝑓: 0.019 ( 29 hom. )

Failed GnomAD Quality Control

Consequence

MESP2
NM_001039958.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.806

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

spondylocostal dysostosis 2, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MESP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 15-89776891-GGGGCAGGGGCAAGGGCAGGGGCAGGGGCAGGGGCAA-G is Benign according to our data. Variant chr15-89776891-GGGGCAGGGGCAAGGGCAGGGGCAGGGGCAGGGGCAA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257242.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 = 0.00894 (534/59704) while in subpopulation NFE AF = 0.0196 (452/23014). AF 95% confidence interval is 0.0181. There are 2 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.549_584delGCAGGGGCAGGGGCAGGGGCAAGGGCAGGGGCAAGG	p.Gln184_Gly195del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000341735.5	NP_001035047.1	Q0VG99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MESP2	ENST00000341735.5 link	c.549_584delGCAGGGGCAGGGGCAGGGGCAAGGGCAGGGGCAAGG	p.Gln184_Gly195del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1159_31-1124delGCAGGGGCAGGGGCAGGGGCAAGGGCAGGGGCAAGG		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1159_39-1124delGCAGGGGCAGGGGCAGGGGCAAGGGCAGGGGCAAGG		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

534

AN:

59648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00302

Gnomad ASJ

AF:

0.000885

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.00266

GnomAD2 exomes

AF:

0.00430

AC:

305

AN:

70850

AF XY:

0.00470

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000894

Gnomad ASJ exome

AF:

0.000513

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00364

Gnomad NFE exome

AF:

0.00892

Gnomad OTH exome

AF:

0.00271

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0189

AC:

8142

AN:

431272

Hom.:

AF XY:

0.0181

AC XY:

3814

AN XY:

211190

show subpopulations

African (AFR)

AF:

0.00150

AC:

AN:

18612

American (AMR)

AF:

0.00340

AC:

AN:

3826

Ashkenazi Jewish (ASJ)

AF:

0.000466

AC:

AN:

6434

East Asian (EAS)

AF:

0.00

AC:

AN:

1180

South Asian (SAS)

AF:

0.000123

AC:

AN:

24372

European-Finnish (FIN)

AF:

0.0169

AC:

120

AN:

7110

Middle Eastern (MID)

AF:

0.000582

AC:

AN:

1718

European-Non Finnish (NFE)

AF:

0.0222

AC:

7793

AN:

350562

Other (OTH)

AF:

0.0104

AC:

181

AN:

17458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

359

718

1078

1437

1796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00894

AC:

534

AN:

59704

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

226

AN XY:

28394

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

26642

American (AMR)

AF:

0.00302

AC:

AN:

3644

Ashkenazi Jewish (ASJ)

AF:

0.000885

AC:

AN:

1130

East Asian (EAS)

AF:

0.00

AC:

AN:

184

South Asian (SAS)

AF:

0.00

AC:

AN:

1712

European-Finnish (FIN)

AF:

0.0108

AC:

AN:

2042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.0196

AC:

452

AN:

23014

Other (OTH)

AF:

0.00264

AC:

AN:

758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00388

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 10, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MESP2: BS1, BS2 -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondylocostal dysostosis 2, autosomal recessive

Benign:1

Sep 25, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

Mutation Taster

=196/4

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over