rs17859889

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004530.6(MMP2):c.832+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,611,964 control chromosomes in the GnomAD database, including 1,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 108 hom., cov: 32)

Exomes 𝑓: 0.025 ( 918 hom. )

Consequence

MMP2
NM_004530.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0370

Publications

5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-55485789-C-T is Benign according to our data. Variant chr16-55485789-C-T is described in ClinVar as Benign. ClinVar VariationId is 319752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP2	NM_004530.6	MANE Select	c.832+12C>T	intron	N/A	NP_004521.1	P08253-1
MMP2	NM_001127891.3		c.682+12C>T	intron	N/A	NP_001121363.1	P08253-3
MMP2	NM_001302508.1		c.604+12C>T	intron	N/A	NP_001289437.1	P08253-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP2	ENST00000219070.9	TSL:1 MANE Select	c.832+12C>T	intron	N/A	ENSP00000219070.4	P08253-1
MMP2	ENST00000437642.6	TSL:1	c.682+12C>T	intron	N/A	ENSP00000394237.2	P08253-3
MMP2	ENST00000570308.5	TSL:1	c.604+12C>T	intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4568

AN:

152088

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0356

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.0777

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0359

GnomAD2 exomes

AF:

0.0405

AC:

10093

AN:

249428

AF XY:

0.0412

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.0977

Gnomad FIN exome

AF:

0.0478

Gnomad NFE exome

AF:

0.0205

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0255

AC:

37197

AN:

1459758

Hom.:

918

Cov.:

AF XY:

0.0271

AC XY:

19704

AN XY:

726188

show subpopulations

African (AFR)

AF:

0.0271

AC:

908

AN:

33450

American (AMR)

AF:

0.0476

AC:

2127

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

1190

AN:

26136

East Asian (EAS)

AF:

0.0863

AC:

3424

AN:

39698

South Asian (SAS)

AF:

0.0752

AC:

6486

AN:

86234

European-Finnish (FIN)

AF:

0.0488

AC:

2536

AN:

51980

Middle Eastern (MID)

AF:

0.0600

AC:

316

AN:

5264

European-Non Finnish (NFE)

AF:

0.0166

AC:

18475

AN:

1111944

Other (OTH)

AF:

0.0288

AC:

1735

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2003

4006

6009

8012

10015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.0301

AC:

4575

AN:

152206

Hom.:

108

Cov.:

AF XY:

0.0330

AC XY:

2455

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0247

AC:

1024

AN:

41526

American (AMR)

AF:

0.0356

AC:

545

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0533

AC:

185

AN:

3472

East Asian (EAS)

AF:

0.100

AC:

516

AN:

5152

South Asian (SAS)

AF:

0.0780

AC:

376

AN:

4820

European-Finnish (FIN)

AF:

0.0461

AC:

489

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0200

AC:

1358

AN:

68000

Other (OTH)

AF:

0.0355

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

219

438

658

877

1096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0259

Hom.:

Bravo

AF:

0.0280

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Multicentric osteolysis nodulosis arthropathy spectrum (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.40

(source)

DANN

Benign

0.60

PhyloP100

0.037

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over