16-55506915-G-T

Variant names:

• chr16-55506915-G-T
• rs243831
• NM_004530.6:c.*1473G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004530.6(MMP2):​c.*1473G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,132 control chromosomes in the GnomAD database, including 57,903 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57903 hom., cov: 31)
• Consequence: MMP2 NM_004530.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.*1473G>T		downstream_gene_variant		ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.*1473G>T		downstream_gene_variant		1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131715 AN: 152014 Hom.: 57881 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.879

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.866 AC: 131780 AN: 152132 Hom.: 57903 Cov.: 31 AF XY: 0.866 AC XY: 64391 AN XY: 74376

African (AFR) AF: 0.699 AC: 28980 AN: 41436

American (AMR) AF: 0.905 AC: 13849 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2998 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4487 AN: 5158

South Asian (SAS) AF: 0.864 AC: 4162 AN: 4818

European-Finnish (FIN) AF: 0.966 AC: 10251 AN: 10610

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64057 AN: 68014

Other (OTH) AF: 0.870 AC: 1841 AN: 2116

Alfa AF: 0.903 Hom.: 119313

Bravo AF: 0.856

Asia WGS AF: 0.804 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs243831; hg19: chr16-55540827;