rs1992116

Variant names:

• chr16-55493979-G-A
• rs1992116
• NM_004530.6:c.1472+686G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55493979-G-A
• chr16-55493979-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.1472+686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,066 control chromosomes in the GnomAD database, including 10,012 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 0.34 (10012 hom., cov: 32)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 28 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.1472+686G>A		intron_variant	Intron 9 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.1472+686G>A		intron_variant	Intron 9 of 12	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51154 AN: 151948 Hom.: 10000 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.336 AC: 51166 AN: 152066 Hom.: 10012 Cov.: 32 AF XY: 0.335 AC XY: 24881 AN XY: 74344

African (AFR) AF: 0.125 AC: 5171 AN: 41498

American (AMR) AF: 0.410 AC: 6266 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1486 AN: 5146

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4017 AN: 10576

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29895 AN: 67966

Other (OTH) AF: 0.356 AC: 752 AN: 2112

Alfa AF: 0.405 Hom.: 17219

Bravo AF: 0.328

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.24
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: rs1992116; hg19: chr16-55527891;