rs1132896

Positions:

chr16-55485623-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004530.6(MMP2):c.678G>C(p.Gly226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,613,650 control chromosomes in the GnomAD database, including 90,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6335 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83932 hom. )

Consequence

MMP2
NM_004530.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0530

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-55485623-G-C is Benign according to our data. Variant chr16-55485623-G-C is described in ClinVar as [Benign]. Clinvar id is 319750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55485623-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.053 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6 linkuse as main transcript	c.678G>C	p.Gly226=	synonymous_variant	5/13	ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9 linkuse as main transcript	c.678G>C	p.Gly226=	synonymous_variant	5/13	1	NM_004530.6	P1	P08253-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39906

AN:

151930

Hom.:

6331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.277

GnomAD3 exomes

AF:

0.305

AC:

76733

AN:

251456

Hom.:

12744

AF XY:

0.307

AC XY:

41762

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0720

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.333

AC:

486678

AN:

1461602

Hom.:

83932

Cov.:

AF XY:

0.332

AC XY:

241140

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0638

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.262

AC:

39901

AN:

152048

Hom.:

6335

Cov.:

AF XY:

0.261

AC XY:

19371

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0746

Gnomad4 AMR

AF:

0.356

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.323

Hom.:

2790

Bravo

AF:

0.257

Asia WGS

AF:

0.180

AC:

625

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.347

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.4

DANN

Benign

0.68

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over