rs11643163

Variant names:

• chr16-55464747-A-G
• rs11643163
• ENST00000570308.5:c.-154A>G

Variant summary

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

The ENST00000570308.5(MMP2):​c.-154A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,028 control chromosomes in the GnomAD database, including 24,238 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 0.56 (24235 hom., cov: 32)
  • Exomes 𝑓: 0.56 (3 hom.)
• Consequence: MMP2 ENST00000570308.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 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.-154A>G		5_prime_UTR_variant	Exon 2 of 14	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85148 AN: 151894 Hom.: 24232 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.563 AC: 9 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.583 AC XY: 7 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 4 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.560 AC: 85195 AN: 152012 Hom.: 24235 Cov.: 32 AF XY: 0.558 AC XY: 41483 AN XY: 74298

African (AFR) AF: 0.449 AC: 18612 AN: 41436

American (AMR) AF: 0.597 AC: 9118 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3294 AN: 5158

South Asian (SAS) AF: 0.547 AC: 2638 AN: 4826

European-Finnish (FIN) AF: 0.597 AC: 6306 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41154 AN: 67954

Other (OTH) AF: 0.579 AC: 1223 AN: 2112

Alfa AF: 0.588 Hom.: 14708

Bravo AF: 0.561

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.23
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11643163; hg19: chr16-55498659;