rs12599775

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1180+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,601,162 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 116 hom., cov: 33)

Exomes 𝑓: 0.015 ( 504 hom. )

Consequence

MMP2
NM_004530.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.14

Publications

6 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=-0.91).

BP6

Variant 16-55489870-G-C is Benign according to our data. Variant chr16-55489870-G-C is described in ClinVar as Benign. ClinVar VariationId is 1248285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0853 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.1180+46G>C	intron	N/A	NP_004521.1	P08253-1
MMP2	NM_001127891.3		c.1030+46G>C	intron	N/A	NP_001121363.1	P08253-3
MMP2	NM_001302508.1		c.952+46G>C	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.1180+46G>C	intron	N/A	ENSP00000219070.4	P08253-1
MMP2	ENST00000437642.6	TSL:1	c.1030+46G>C	intron	N/A	ENSP00000394237.2	P08253-3
MMP2	ENST00000570308.5	TSL:1	c.952+46G>C	intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4482

AN:

152098

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0566

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.0919

Gnomad SAS

AF:

0.0435

Gnomad FIN

AF:

0.00715

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00770

Gnomad OTH

AF:

0.0321

GnomAD2 exomes

AF:

0.0314

AC:

7196

AN:

229068

AF XY:

0.0298

show subpopulations

Gnomad AFR exome

AF:

0.0599

Gnomad AMR exome

AF:

0.0636

Gnomad ASJ exome

AF:

0.0396

Gnomad EAS exome

AF:

0.0982

Gnomad FIN exome

AF:

0.00769

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0149

AC:

21580

AN:

1448946

Hom.:

504

Cov.:

AF XY:

0.0155

AC XY:

11167

AN XY:

720316

show subpopulations

African (AFR)

AF:

0.0585

AC:

1944

AN:

33222

American (AMR)

AF:

0.0619

AC:

2655

AN:

42898

Ashkenazi Jewish (ASJ)

AF:

0.0402

AC:

1044

AN:

25942

East Asian (EAS)

AF:

0.0942

AC:

3708

AN:

39346

South Asian (SAS)

AF:

0.0404

AC:

3441

AN:

85238

European-Finnish (FIN)

AF:

0.00699

AC:

355

AN:

50816

Middle Eastern (MID)

AF:

0.0209

AC:

106

AN:

5074

European-Non Finnish (NFE)

AF:

0.00638

AC:

7057

AN:

1106438

Other (OTH)

AF:

0.0212

AC:

1270

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1145

2290

3434

4579

5724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.0295

AC:

4488

AN:

152216

Hom.:

116

Cov.:

AF XY:

0.0301

AC XY:

2236

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0565

AC:

2346

AN:

41534

American (AMR)

AF:

0.0409

AC:

626

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3472

East Asian (EAS)

AF:

0.0921

AC:

474

AN:

5144

South Asian (SAS)

AF:

0.0434

AC:

209

AN:

4820

European-Finnish (FIN)

AF:

0.00715

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00771

AC:

524

AN:

68006

Other (OTH)

AF:

0.0322

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

224

449

673

898

1122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0221

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.017

(source)

DANN

Benign

0.48

PhyloP100

-5.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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