rs243839

Variant names:

• chr16-55495499-G-A
• rs243839
• NM_004530.6:c.1473-1427G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55495499-G-A
• chr16-55495499-G-C

Variant summary

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

The NM_004530.6(MMP2):​c.1473-1427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,176 control chromosomes in the GnomAD database, including 39,619 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 0.70 (39619 hom., cov: 33)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004530.6. 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
	MMP2	NM_004530.6	MANE Select	c.1473-1427G>A		intron	N/A	NP_004521.1
	MMP2	NM_001127891.3		c.1323-1427G>A		intron	N/A	NP_001121363.1
	MMP2	NM_001302508.1		c.1245-1427G>A		intron	N/A	NP_001289437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000219070.9	TSL:1 MANE Select	c.1473-1427G>A		intron	N/A	ENSP00000219070.4
	MMP2	ENST00000437642.6	TSL:1	c.1323-1427G>A		intron	N/A	ENSP00000394237.2
	MMP2	ENST00000570308.5	TSL:1	c.1245-1427G>A		intron	N/A	ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107225 AN: 152058 Hom.: 39612 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.705 AC: 107267 AN: 152176 Hom.: 39619 Cov.: 33 AF XY: 0.706 AC XY: 52524 AN XY: 74390

African (AFR) AF: 0.471 AC: 19544 AN: 41478

American (AMR) AF: 0.726 AC: 11109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3472

East Asian (EAS) AF: 0.590 AC: 3051 AN: 5172

South Asian (SAS) AF: 0.768 AC: 3702 AN: 4822

European-Finnish (FIN) AF: 0.829 AC: 8779 AN: 10590

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56024 AN: 68026

Other (OTH) AF: 0.698 AC: 1476 AN: 2116

Alfa AF: 0.745 Hom.: 7617

Bravo AF: 0.686

Asia WGS AF: 0.668 AC: 2319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs243839; hg19: chr16-55529411;