16-55462617-C-A

Variant names:

• chr16-55462617-C-A
• rs1816595
• ENST00000570308.5:c.-349-1935C>A

Variant summary

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

The ENST00000570308.5(MMP2):​c.-349-1935C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,928 control chromosomes in the GnomAD database, including 18,167 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 0.48 (18167 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000570308.5	TSL:1	c.-349-1935C>A		intron	N/A	ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72433 AN: 151810 Hom.: 18165 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.477 AC: 72459 AN: 151928 Hom.: 18167 Cov.: 31 AF XY: 0.478 AC XY: 35491 AN XY: 74222

African (AFR) AF: 0.307 AC: 12726 AN: 41436

American (AMR) AF: 0.548 AC: 8371 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3086 AN: 5128

South Asian (SAS) AF: 0.471 AC: 2271 AN: 4824

European-Finnish (FIN) AF: 0.573 AC: 6019 AN: 10510

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36301 AN: 67974

Other (OTH) AF: 0.510 AC: 1076 AN: 2110

Alfa AF: 0.516 Hom.: 26065

Bravo AF: 0.475

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.69
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1816595; hg19: chr16-55496529;