ENST00000570308.5:c.-75-5284G>A

Variant names:

• chr16-55477625-G-A
• rs243866
• ENST00000570308.5:c.-75-5284G>A

Variant summary

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

The ENST00000570308.5(MMP2):​c.-75-5284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,844 control chromosomes in the GnomAD database, including 3,225 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 0.19 (3225 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 102 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000570308.5	TSL:1	c.-75-5284G>A		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28142 AN: 151726 Hom.: 3228 Cov.: 31

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.185 AC: 28136 AN: 151844 Hom.: 3225 Cov.: 31 AF XY: 0.186 AC XY: 13836 AN XY: 74198

African (AFR) AF: 0.0572 AC: 2368 AN: 41418

American (AMR) AF: 0.211 AC: 3220 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3472

East Asian (EAS) AF: 0.105 AC: 541 AN: 5158

South Asian (SAS) AF: 0.150 AC: 718 AN: 4798

European-Finnish (FIN) AF: 0.290 AC: 3051 AN: 10524

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16895 AN: 67918

Other (OTH) AF: 0.180 AC: 380 AN: 2110

Alfa AF: 0.213 Hom.: 7570

Bravo AF: 0.172

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.62
PhyloP100		-1.3
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: rs243866; hg19: chr16-55511537;