rs11541998

Positions:

Variant summary

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

The ENST00000219070.9(MMP2):c.1842C>G(p.Pro614=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 1,613,442 control chromosomes in the GnomAD database, including 8,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P614P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.073 ( 511 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8407 hom. )

Consequence

MMP2
ENST00000219070.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.46

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=-0.81).

BP6

Variant 16-55502851-C-G is Benign according to our data. Variant chr16-55502851-C-G is described in ClinVar as [Benign]. Clinvar id is 319769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP2	NM_004530.6 linkuse as main transcript	c.1842C>G	p.Pro614=	synonymous_variant	12/13	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9 linkuse as main transcript	c.1842C>G	p.Pro614=	synonymous_variant	12/13	1	NM_004530.6	ENSP00000219070	P1	P08253-1

Frequencies

GnomAD3 genomes

AF:

0.0736

AC:

11196

AN:

152158

Hom.:

511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0728

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0464

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0794

GnomAD3 exomes

AF:

0.0770

AC:

19332

AN:

251108

Hom.:

978

AF XY:

0.0787

AC XY:

10677

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0448

Gnomad FIN exome

AF:

0.0785

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.0941

GnomAD4 exome

AF:

0.101

AC:

148098

AN:

1461166

Hom.:

8407

Cov.:

AF XY:

0.0996

AC XY:

72387

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.0613

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0475

Gnomad4 FIN exome

AF:

0.0804

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.0921

GnomAD4 genome

AF:

0.0735

AC:

11191

AN:

152276

Hom.:

511

Cov.:

AF XY:

0.0703

AC XY:

5233

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.0726

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0468

Gnomad4 FIN

AF:

0.0763

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0781

Alfa

AF:

0.0821

Hom.:

229

Bravo

AF:

0.0714

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.81

CADD

Benign

0.0080

DANN

Benign

0.51

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

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