16-55489793-T-C

Position:

chr16-55489793-T-C

Variant summary

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

The NM_004530.6(MMP2):c.1149T>C(p.Asp383Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,613,924 control chromosomes in the GnomAD database, including 573,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49578 hom., cov: 32)

Exomes 𝑓: 0.85 ( 523749 hom. )

Consequence

MMP2
NM_004530.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.12

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=-0.84).

BP6

Variant 16-55489793-T-C is Benign according to our data. Variant chr16-55489793-T-C is described in ClinVar as [Benign]. Clinvar id is 319756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55489793-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 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.1149T>C	p.Asp383Asp	synonymous_variant	7/13	ENST00000219070.9	NP_004521.1	P08253-1A0A024R6R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9 linkuse as main transcript	c.1149T>C	p.Asp383Asp	synonymous_variant	7/13	1	NM_004530.6	ENSP00000219070.4		P08253-1

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122407

AN:

151982

Hom.:

49547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.866

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.787

GnomAD3 exomes

AF:

0.837

AC:

210387

AN:

251362

Hom.:

88319

AF XY:

0.842

AC XY:

114377

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.711

Gnomad AMR exome

AF:

0.824

Gnomad ASJ exome

AF:

0.821

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.893

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.828

GnomAD4 exome

AF:

0.846

AC:

1236497

AN:

1461824

Hom.:

523749

Cov.:

AF XY:

0.847

AC XY:

616245

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.704

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.822

Gnomad4 EAS exome

AF:

0.810

Gnomad4 SAS exome

AF:

0.892

Gnomad4 FIN exome

AF:

0.866

Gnomad4 NFE exome

AF:

0.850

Gnomad4 OTH exome

AF:

0.830

GnomAD4 genome

AF:

0.805

AC:

122491

AN:

152100

Hom.:

49578

Cov.:

AF XY:

0.809

AC XY:

60167

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.835

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.887

Gnomad4 FIN

AF:

0.876

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.787

Alfa

AF:

0.832

Hom.:

60215

Bravo

AF:

0.795

Asia WGS

AF:

0.825

AC:

2866

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Multicentric osteolysis nodulosis arthropathy spectrum

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.11

DANN

Benign

0.42

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