rs1053605

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.750C>T(p.Thr250Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 1,614,064 control chromosomes in the GnomAD database, including 4,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 356 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4355 hom. )

Consequence

MMP2
NM_004530.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.00

Publications

46 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=-0.85).

BP6

Variant 16-55485695-C-T is Benign according to our data. Variant chr16-55485695-C-T is described in ClinVar as Benign. ClinVar VariationId is 319751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6 link	c.750C>T	p.Thr250Thr	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.750C>T	p.Thr250Thr	synonymous_variant	Exon 5 of 13	1	NM_004530.6	ENSP00000219070.4		P08253-1

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9661

AN:

152090

Hom.:

349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0525

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0698

Gnomad OTH

AF:

0.0651

GnomAD2 exomes

AF:

0.0726

AC:

18249

AN:

251482

AF XY:

0.0759

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.0324

Gnomad ASJ exome

AF:

0.0614

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0521

Gnomad NFE exome

AF:

0.0679

Gnomad OTH exome

AF:

0.0663

GnomAD4 exome

AF:

0.0731

AC:

106793

AN:

1461856

Hom.:

4355

Cov.:

AF XY:

0.0747

AC XY:

54312

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0491

AC:

1644

AN:

33476

American (AMR)

AF:

0.0354

AC:

1585

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0598

AC:

1564

AN:

26134

East Asian (EAS)

AF:

0.147

AC:

5827

AN:

39700

South Asian (SAS)

AF:

0.120

AC:

10332

AN:

86258

European-Finnish (FIN)

AF:

0.0504

AC:

2690

AN:

53420

Middle Eastern (MID)

AF:

0.0638

AC:

368

AN:

5768

European-Non Finnish (NFE)

AF:

0.0702

AC:

78070

AN:

1111984

Other (OTH)

AF:

0.0780

AC:

4713

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

6360

12720

19080

25440

31800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2990

5980

8970

11960

14950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0636

AC:

9679

AN:

152208

Hom.:

356

Cov.:

AF XY:

0.0642

AC XY:

4775

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0451

AC:

1873

AN:

41526

American (AMR)

AF:

0.0453

AC:

693

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

202

AN:

3472

East Asian (EAS)

AF:

0.146

AC:

754

AN:

5164

South Asian (SAS)

AF:

0.128

AC:

615

AN:

4818

European-Finnish (FIN)

AF:

0.0525

AC:

557

AN:

10614

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0698

AC:

4745

AN:

67996

Other (OTH)

AF:

0.0734

AC:

155

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

475

950

1424

1899

2374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0689

Hom.:

792

Bravo

AF:

0.0619

Asia WGS

AF:

0.168

AC:

582

AN:

3478

EpiCase

AF:

0.0704

EpiControl

AF:

0.0742

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0050

(source)

DANN

Benign

0.55

PhyloP100

-2.0

Mutation Taster

=98/2

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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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