Genetic Variant NM_001039958.2:c.546_557delAGGGCAGGGGCA (chr15-89776891-GGGGCAGGGGCAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001039958.2(MESP2):c.546_557delAGGGCAGGGGCA(p.Gly183_Gln186del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 491,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

MESP2
NM_001039958.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.806

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP2	NM_001039958.2 link	c.546_557delAGGGCAGGGGCA	p.Gly183_Gln186del	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.546_557delAGGGCAGGGGCA	p.Gly183_Gln186del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_001039958.2	ENSP00000342392.3	Q0VG99
MESP2	ENST00000560219.2 link	c.31-1162_31-1151delAGGGCAGGGGCA		intron_variant	Intron 2 of 2	1		ENSP00000452998.1	H0YKZ5
MESP2	ENST00000558723.1 link	n.39-1162_39-1151delAGGGCAGGGGCA		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.000101

AC:

AN:

59652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000434

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000141

AC:

AN:

70850

AF XY:

0.0000263

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000348

AC:

AN:

431298

Hom.:

AF XY:

0.0000473

AC XY:

AN XY:

211200

show subpopulations

African (AFR)

AF:

0.0000537

AC:

AN:

18614

American (AMR)

AF:

0.00

AC:

AN:

3826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6434

East Asian (EAS)

AF:

0.00

AC:

AN:

1180

South Asian (SAS)

AF:

0.00

AC:

AN:

24372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1718

European-Non Finnish (NFE)

AF:

0.0000371

AC:

AN:

350584

Other (OTH)

AF:

0.0000573

AC:

AN:

17460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000100

AC:

AN:

59708

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

28396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26642

American (AMR)

AF:

0.00137

AC:

AN:

3644

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

0.00

AC:

AN:

2042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.0000434

AC:

AN:

23018

Other (OTH)

AF:

0.00

AC:

AN:

758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 2, autosomal recessive

Uncertain:1

Sep 12, 2017

Counsyl

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

Mutation Taster

=189/11

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over