16-55505279-C-G

Variant names:

• chr16-55505279-C-G
• rs243832
• NM_004530.6:c.1880-60C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004530.6(MMP2):​c.1880-60C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,403,922 control chromosomes in the GnomAD database, including 175,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19226 hom., cov: 31)
  • Exomes 𝑓: 0.50 (155808 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.105
• Publications: 24 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-55505279-C-G is Benign according to our data. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55505279-C-G is described in CliVar as Benign. Clinvar id is 1234221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.1880-60C>G		intron_variant	Intron 12 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.1880-60C>G		intron_variant	Intron 12 of 12	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76271 AN: 151782 Hom.: 19219 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.497 AC: 622035 AN: 1252022 Hom.: 155808 AF XY: 0.496 AC XY: 314722 AN XY: 633954

African (AFR) AF: 0.514 AC: 15064 AN: 29304

American (AMR) AF: 0.488 AC: 21690 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12275 AN: 24794

East Asian (EAS) AF: 0.630 AC: 24345 AN: 38644

South Asian (SAS) AF: 0.518 AC: 42535 AN: 82168

European-Finnish (FIN) AF: 0.565 AC: 30064 AN: 53242

Middle Eastern (MID) AF: 0.432 AC: 2325 AN: 5382

European-Non Finnish (NFE) AF: 0.486 AC: 447387 AN: 920738

Other (OTH) AF: 0.494 AC: 26350 AN: 53308

GnomAD4 genome AF: 0.502 AC: 76303 AN: 151900 Hom.: 19226 Cov.: 31 AF XY: 0.506 AC XY: 37539 AN XY: 74222

African (AFR) AF: 0.517 AC: 21414 AN: 41410

American (AMR) AF: 0.466 AC: 7113 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1657 AN: 3462

East Asian (EAS) AF: 0.642 AC: 3302 AN: 5146

South Asian (SAS) AF: 0.532 AC: 2563 AN: 4822

European-Finnish (FIN) AF: 0.569 AC: 5999 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32805 AN: 67940

Other (OTH) AF: 0.478 AC: 1004 AN: 2100

Alfa AF: 0.482 Hom.: 2167

Bravo AF: 0.496

Asia WGS AF: 0.565 AC: 1969 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		-0.10
Mutation Taster		=2/98	disease causing

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

Other links and lift over

dbSNP: rs243832; hg19: chr16-55539191; COSMIC: COSV50894590; COSMIC: COSV50894590;