rs2285053

Variant names:

• chr16-55478465-C-T
• rs2285053
• ENST00000570308.5:c.-75-4444C>T

Variant summary

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

The ENST00000570308.5(MMP2):​c.-75-4444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,084 control chromosomes in the GnomAD database, including 1,259 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 0.12 (1259 hom., cov: 32)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526
• Publications: 211 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-75-4444C>T		intron_variant	Intron 2 of 13	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18739 AN: 151966 Hom.: 1262 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.123 AC: 18738 AN: 152084 Hom.: 1259 Cov.: 32 AF XY: 0.123 AC XY: 9170 AN XY: 74338

African (AFR) AF: 0.114 AC: 4734 AN: 41478

American (AMR) AF: 0.165 AC: 2528 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1328 AN: 5140

South Asian (SAS) AF: 0.109 AC: 526 AN: 4812

European-Finnish (FIN) AF: 0.0925 AC: 981 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7567 AN: 67982

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.118 Hom.: 1502

Bravo AF: 0.132

Asia WGS AF: 0.166 AC: 579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.5
DANN	Benign	0.92
PhyloP100		0.53
PromoterAI		0.0067	Neutral
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: rs2285053; hg19: chr16-55512377;