16-55484698-C-T

Variant names:

• chr16-55484698-C-T
• rs17301608
• NM_004530.6:c.529+534C>T

Variant summary

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

The NM_004530.6(MMP2):​c.529+534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,952 control chromosomes in the GnomAD database, including 12,027 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 0.40 (12027 hom., cov: 32)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 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.529+534C>T		intron	N/A	NP_004521.1
	MMP2	NM_001127891.3		c.379+534C>T		intron	N/A	NP_001121363.1
	MMP2	NM_001302508.1		c.301+534C>T		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.529+534C>T		intron	N/A	ENSP00000219070.4
	MMP2	ENST00000437642.6	TSL:1	c.379+534C>T		intron	N/A	ENSP00000394237.2
	MMP2	ENST00000570308.5	TSL:1	c.301+534C>T		intron	N/A	ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60497 AN: 151834 Hom.: 12002 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.399 AC: 60558 AN: 151952 Hom.: 12027 Cov.: 32 AF XY: 0.398 AC XY: 29575 AN XY: 74274

African (AFR) AF: 0.434 AC: 17957 AN: 41398

American (AMR) AF: 0.454 AC: 6944 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1798 AN: 5142

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4818

European-Finnish (FIN) AF: 0.363 AC: 3838 AN: 10566

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.378 AC: 25683 AN: 67968

Other (OTH) AF: 0.394 AC: 830 AN: 2108

Alfa AF: 0.380 Hom.: 46720

Bravo AF: 0.407

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.40
PhyloP100		-0.92
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: rs17301608; hg19: chr16-55518610;