chr16-55479277-T-TGCG
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_004530.6(MMP2):c.-183_-181dupCGG variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000722 in 401,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
MMP2
NM_004530.6 5_prime_UTR
NM_004530.6 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.69
Publications
0 publications found
Genes affected
MMP2 (HGNC:7166): (matrix metallopeptidase 2) This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
MMP2 Gene-Disease associations (from GenCC):
- multicentric osteolysis, nodulosis, and arthropathyInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- multicentric osteolysis-nodulosis-arthropathy spectrumInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MMP2 | NM_004530.6 | c.-183_-181dupCGG | 5_prime_UTR_variant | Exon 1 of 13 | ENST00000219070.9 | NP_004521.1 | ||
| MMP2 | NM_001302508.1 | c.-76+332_-76+334dupCGG | intron_variant | Intron 1 of 12 | NP_001289437.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MMP2 | ENST00000219070.9 | c.-183_-181dupCGG | 5_prime_UTR_variant | Exon 1 of 13 | 1 | NM_004530.6 | ENSP00000219070.4 | |||
| MMP2 | ENST00000570308.5 | c.-75-3612_-75-3610dupCGG | intron_variant | Intron 2 of 13 | 1 | ENSP00000461421.1 | ||||
| MMP2 | ENST00000568715.5 | c.-76+332_-76+334dupCGG | intron_variant | Intron 1 of 3 | 4 | ENSP00000457949.1 |
Frequencies
GnomAD3 genomes 0.0000992 AC: 15AN: 151274Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
15
AN:
151274
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000560 AC: 14AN: 250018Hom.: 0 Cov.: 4 AF XY: 0.0000630 AC XY: 8AN XY: 126950 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
250018
Hom.:
Cov.:
4
AF XY:
AC XY:
8
AN XY:
126950
show subpopulations
African (AFR)
AF:
AC:
1
AN:
5860
American (AMR)
AF:
AC:
1
AN:
5234
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
6518
East Asian (EAS)
AF:
AC:
1
AN:
16292
South Asian (SAS)
AF:
AC:
1
AN:
4122
European-Finnish (FIN)
AF:
AC:
1
AN:
17358
Middle Eastern (MID)
AF:
AC:
1
AN:
1082
European-Non Finnish (NFE)
AF:
AC:
8
AN:
179686
Other (OTH)
AF:
AC:
0
AN:
13866
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.418
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000991 AC: 15AN: 151370Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9AN XY: 73976 show subpopulations
GnomAD4 genome
AF:
AC:
15
AN:
151370
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
73976
show subpopulations
African (AFR)
AF:
AC:
4
AN:
41362
American (AMR)
AF:
AC:
3
AN:
15220
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
2
AN:
5118
South Asian (SAS)
AF:
AC:
1
AN:
4802
European-Finnish (FIN)
AF:
AC:
0
AN:
10382
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
5
AN:
67724
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Multicentric Osteolysis-Nodulosis-Arthropathy (MONA) Spectrum Disorders Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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