chr16-55485623-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004530.6(MMP2):c.678G>C(p.Gly226Gly) 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:5

Conservation

PhyloP100: -0.0530

Publications

37 publications found

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 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

MMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
MMP2	NM_004530.6 link	c.678G>C	p.Gly226Gly	synonymous_variant	Exon 5 of 13	ENST00000219070.9	NP_004521.1	P08253-1A0A024R6R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9 link	c.678G>C	p.Gly226Gly	synonymous_variant	Exon 5 of 13	1	NM_004530.6	ENSP00000219070.4		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

GnomAD2 exomes

AF:

0.305

AC:

76733

AN:

251456

AF XY:

0.307

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 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

African (AFR)

AF:

0.0638

AC:

2137

AN:

33480

American (AMR)

AF:

0.365

AC:

16317

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6663

AN:

26136

East Asian (EAS)

AF:

0.162

AC:

6430

AN:

39700

South Asian (SAS)

AF:

0.266

AC:

22950

AN:

86246

European-Finnish (FIN)

AF:

0.316

AC:

16879

AN:

53420

Middle Eastern (MID)

AF:

0.319

AC:

1837

AN:

5764

European-Non Finnish (NFE)

AF:

0.355

AC:

394827

AN:

1111742

Other (OTH)

AF:

0.309

AC:

18638

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

19923

39846

59768

79691

99614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.262

AC:

39901

AN:

152048

Hom.:

6335

Cov.:

AF XY:

0.261

AC XY:

19371

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0746

AC:

3095

AN:

41506

American (AMR)

AF:

0.356

AC:

5434

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

896

AN:

3468

East Asian (EAS)

AF:

0.147

AC:

757

AN:

5158

South Asian (SAS)

AF:

0.249

AC:

1198

AN:

4808

European-Finnish (FIN)

AF:

0.314

AC:

3323

AN:

10584

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24081

AN:

67952

Other (OTH)

AF:

0.273

AC:

576

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1415

2830

4245

5660

7075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.4

(source)

DANN

Benign

0.68

PhyloP100

-0.053

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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chr16-55485623-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over