rs2287074

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_004530.6(MMP2):c.1380G>A(p.Thr460Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,613,572 control chromosomes in the GnomAD database, including 143,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10744 hom., cov: 31)

Exomes 𝑓: 0.42 ( 133162 hom. )

Consequence

MMP2
NM_004530.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.24

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=-0.63).

BP6

Variant 16-55493201-G-A is Benign according to our data. Variant chr16-55493201-G-A is described in ClinVar as [Benign]. Clinvar id is 319761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55493201-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6 link	c.1380G>A	p.Thr460Thr	synonymous_variant	Exon 9 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.1380G>A	p.Thr460Thr	synonymous_variant	Exon 9 of 13	1	NM_004530.6	ENSP00000219070.4		P08253-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55027

AN:

151742

Hom.:

10732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.372

GnomAD3 exomes

AF:

0.393

AC:

98853

AN:

251404

Hom.:

20086

AF XY:

0.397

AC XY:

53948

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.424

AC:

619177

AN:

1461712

Hom.:

133162

Cov.:

AF XY:

0.423

AC XY:

307693

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.363

AC:

55054

AN:

151860

Hom.:

10744

Cov.:

AF XY:

0.360

AC XY:

26720

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.418

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.440

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.424

Hom.:

25974

Bravo

AF:

0.359

Asia WGS

AF:

0.353

AC:

1227

AN:

3478

EpiCase

AF:

0.436

EpiControl

AF:

0.438

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.63

CADD

Benign

1.2

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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