ENST00000570308.5:c.-75-6362T>G

Variant names:

• chr16-55476547-T-G
• rs11643630
• ENST00000570308.5:c.-75-6362T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570308.5(MMP2):​c.-75-6362T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,086 control chromosomes in the GnomAD database, including 23,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23589 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 11 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 arthropathy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000570308.5	TSL:1	c.-75-6362T>G		intron	N/A	ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84222 AN: 151968 Hom.: 23586 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.540

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 84263 AN: 152086 Hom.: 23589 Cov.: 33 AF XY: 0.554 AC XY: 41159 AN XY: 74332

African (AFR) AF: 0.478 AC: 19826 AN: 41486

American (AMR) AF: 0.522 AC: 7979 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2231 AN: 5156

South Asian (SAS) AF: 0.645 AC: 3103 AN: 4812

European-Finnish (FIN) AF: 0.557 AC: 5893 AN: 10578

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.609 AC: 41368 AN: 67978

Other (OTH) AF: 0.543 AC: 1149 AN: 2116

Alfa AF: 0.572 Hom.: 4252

Bravo AF: 0.542

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.2
DANN	Benign	0.94
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11643630; hg19: chr16-55510459;