ENST00000570308.5:c.-75-6826C>T

Variant names:

• chr16-55476083-C-T
• rs7189232
• ENST00000570308.5:c.-75-6826C>T

Variant summary

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

The ENST00000570308.5(MMP2):​c.-75-6826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,142 control chromosomes in the GnomAD database, including 151 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 0.033 (151 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0691 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.-75-6826C>T		intron_variant	Intron 2 of 13	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 4996 AN: 152022 Hom.: 150 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00966

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0329 AC: 5002 AN: 152142 Hom.: 151 Cov.: 33 AF XY: 0.0335 AC XY: 2495 AN XY: 74390

African (AFR) AF: 0.0712 AC: 2956 AN: 41490

American (AMR) AF: 0.0124 AC: 190 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3468

East Asian (EAS) AF: 0.00968 AC: 50 AN: 5166

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4824

European-Finnish (FIN) AF: 0.0493 AC: 523 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0154 AC: 1044 AN: 67996

Other (OTH) AF: 0.0275 AC: 58 AN: 2110

Alfa AF: 0.0262 Hom.: 27

Bravo AF: 0.0322

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.56
PhyloP100		0.39
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: rs7189232; hg19: chr16-55509995;