chr16-55479584-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The NM_004530.6(MMP2):c.105C>T(p.Ile35Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
MMP2
NM_004530.6 synonymous
NM_004530.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.26
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 Likely_benign. Variant got -6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 16-55479584-C-T is Benign according to our data. Variant chr16-55479584-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193285.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=1.26 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000526 (8/152232) while in subpopulation EAS AF= 0.000966 (5/5178). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MMP2 | NM_004530.6 | c.105C>T | p.Ile35Ile | synonymous_variant | 1/13 | ENST00000219070.9 | NP_004521.1 | |
| MMP2 | NM_001302508.1 | c.-76+619C>T | intron_variant | NP_001289437.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MMP2 | ENST00000219070.9 | c.105C>T | p.Ile35Ile | synonymous_variant | 1/13 | 1 | NM_004530.6 | ENSP00000219070.4 | ||
| MMP2 | ENST00000570308.5 | c.-75-3325C>T | intron_variant | 1 | ENSP00000461421.1 | |||||
| MMP2 | ENST00000568715.5 | c.-76+619C>T | intron_variant | 4 | ENSP00000457949.1 |
Frequencies
GnomAD3 genomes 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249572Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135486
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GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461358Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 726990
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GnomAD4 genome 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74364
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 20, 2015 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 22, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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