chr16-55475122-G-A

Variant names:

• chr16-55475122-G-A
• rs11644561
• ENST00000570308.5:c.-75-7787G>A

Variant summary

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

The ENST00000570308.5(MMP2):​c.-75-7787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,104 control chromosomes in the GnomAD database, including 3,276 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 0.20 (3276 hom., cov: 32)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 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.-75-7787G>A		intron_variant	Intron 2 of 13	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30461 AN: 151986 Hom.: 3266 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.200 AC: 30493 AN: 152104 Hom.: 3276 Cov.: 32 AF XY: 0.195 AC XY: 14478 AN XY: 74358

African (AFR) AF: 0.277 AC: 11497 AN: 41476

American (AMR) AF: 0.170 AC: 2596 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5164

South Asian (SAS) AF: 0.124 AC: 599 AN: 4824

European-Finnish (FIN) AF: 0.159 AC: 1682 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12426 AN: 67970

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.194 Hom.: 548

Bravo AF: 0.206

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.088
DANN	Benign	0.63
PhyloP100		-0.99
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: rs11644561; hg19: chr16-55509034;