16-55466082-T-C

Variant names:

• chr16-55466082-T-C
• rs7187242
• ENST00000570308.5:c.-76+1257T>C

Variant summary

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

The ENST00000570308.5(MMP2):​c.-76+1257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,120 control chromosomes in the GnomAD database, including 3,907 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 0.21 (3907 hom., cov: 32)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.03
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 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.-76+1257T>C		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32635 AN: 152002 Hom.: 3902 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.0958

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.215 AC: 32675 AN: 152120 Hom.: 3907 Cov.: 32 AF XY: 0.221 AC XY: 16426 AN XY: 74340

African (AFR) AF: 0.196 AC: 8138 AN: 41498

American (AMR) AF: 0.286 AC: 4368 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0958 AC: 332 AN: 3466

East Asian (EAS) AF: 0.517 AC: 2670 AN: 5162

South Asian (SAS) AF: 0.203 AC: 978 AN: 4826

European-Finnish (FIN) AF: 0.310 AC: 3276 AN: 10560

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12361 AN: 67998

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.190 Hom.: 8491

Bravo AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.57
PhyloP100		-4.0
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: rs7187242; hg19: chr16-55499994;