rs11859163

Variant names:

• chr16-55468464-T-G
• rs11859163
• ENST00000570308.5:c.-76+3639T>G

Variant summary

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

The ENST00000570308.5(MMP2):​c.-76+3639T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,066 control chromosomes in the GnomAD database, including 10,498 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 0.36 (10498 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 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.-76+3639T>G		intron_variant	Intron 2 of 13	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55194 AN: 151948 Hom.: 10500 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.363 AC: 55214 AN: 152066 Hom.: 10498 Cov.: 31 AF XY: 0.353 AC XY: 26257 AN XY: 74328

African (AFR) AF: 0.364 AC: 15080 AN: 41462

American (AMR) AF: 0.299 AC: 4572 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3468

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5178

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10586

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27871 AN: 67952

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.395 Hom.: 54438

Bravo AF: 0.364

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.72
PhyloP100		-0.67
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: rs11859163; hg19: chr16-55502376;