rs12599775
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_004530.6(MMP2):c.1180+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,601,162 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.029 ( 116 hom., cov: 33)
Exomes 𝑓: 0.015 ( 504 hom. )
Consequence
MMP2
NM_004530.6 intron
NM_004530.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.14
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 16-55489870-G-C is Benign according to our data. Variant chr16-55489870-G-C is described in ClinVar as [Benign]. Clinvar id is 1248285.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMP2 | NM_004530.6 | c.1180+46G>C | intron_variant | ENST00000219070.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMP2 | ENST00000219070.9 | c.1180+46G>C | intron_variant | 1 | NM_004530.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0295 AC: 4482AN: 152098Hom.: 116 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0314 AC: 7196AN: 229068Hom.: 216 AF XY: 0.0298 AC XY: 3694AN XY: 124114
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GnomAD4 exome AF: 0.0149 AC: 21580AN: 1448946Hom.: 504 Cov.: 32 AF XY: 0.0155 AC XY: 11167AN XY: 720316
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GnomAD4 genome ? AF: 0.0295 AC: 4488AN: 152216Hom.: 116 Cov.: 33 AF XY: 0.0301 AC XY: 2236AN XY: 74402
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at