rs243865
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000570308.5(MMP2):c.-75-5015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,156 control chromosomes in the GnomAD database, including 3,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).
Frequency
Genomes: 𝑓 0.19 ( 3255 hom., cov: 32)
Consequence
MMP2
ENST00000570308.5 intron
ENST00000570308.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.93
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MMP2 | ENST00000570308.5 | c.-75-5015C>T | intron_variant | 1 | ENSP00000461421 |
Frequencies
GnomAD3 genomes 0.187 AC: 28505AN: 152036Hom.: 3258 Cov.: 32
GnomAD3 genomes
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.187 AC: 28505AN: 152156Hom.: 3255 Cov.: 32 AF XY: 0.189 AC XY: 14021AN XY: 74360
GnomAD4 genome
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14021
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Asia WGS
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426
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3478
ClinVar
Significance: association
Submissions summary: Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lip and oral cavity carcinoma Other:1
| association, criteria provided, single submitter | case-control | Department of Biological Science, Sunandan Divatia School of Science, NMIMS University | Jan 01, 2016 | The heterozygous (CT) genotype showed a higher frequency in cases as compared to controls and a significant association was observed with an OR of 1.469 (1.13-1.90). The homozygous WT (CC) genotype indicated decreased risk to oral cancer with an OR 0.669 (0.51-0.86) - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at