ENST00000570308.5:c.-75-7948A>T

Variant names:

• chr16-55474961-A-T
• rs1116195
• ENST00000570308.5:c.-75-7948A>T

Variant summary

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

The ENST00000570308.5(MMP2):​c.-75-7948A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,100 control chromosomes in the GnomAD database, including 25,013 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 0.57 (25013 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 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.-75-7948A>T		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87173 AN: 151982 Hom.: 25005 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.573 AC: 87226 AN: 152100 Hom.: 25013 Cov.: 33 AF XY: 0.569 AC XY: 42310 AN XY: 74356

African (AFR) AF: 0.554 AC: 22961 AN: 41482

American (AMR) AF: 0.582 AC: 8905 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2797 AN: 5168

South Asian (SAS) AF: 0.496 AC: 2394 AN: 4826

European-Finnish (FIN) AF: 0.581 AC: 6142 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39972 AN: 67972

Other (OTH) AF: 0.584 AC: 1234 AN: 2114

Alfa AF: 0.576 Hom.: 3136

Bravo AF: 0.578

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.31
PhyloP100		-1.2
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: rs1116195; hg19: chr16-55508873;