16-55490564-A-G

Variant names:

• chr16-55490564-A-G
• rs2192852
• NM_004530.6:c.1180+740A>G

Variant summary

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

The NM_004530.6(MMP2):​c.1180+740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,978 control chromosomes in the GnomAD database, including 12,159 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 (12159 hom., cov: 32)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.1180+740A>G		intron_variant	Intron 7 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.1180+740A>G		intron_variant	Intron 7 of 12	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60923 AN: 151860 Hom.: 12141 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.401 AC: 60966 AN: 151978 Hom.: 12159 Cov.: 32 AF XY: 0.400 AC XY: 29738 AN XY: 74284

African (AFR) AF: 0.395 AC: 16352 AN: 41390

American (AMR) AF: 0.464 AC: 7094 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1261 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1756 AN: 5154

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4812

European-Finnish (FIN) AF: 0.378 AC: 4001 AN: 10592

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27290 AN: 67960

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.403 Hom.: 2711

Bravo AF: 0.408

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.75
PhyloP100		0.57
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: rs2192852; hg19: chr16-55524476;