rs2576561

Variant names:

• chr16-55437062-T-C
• rs2576561
• ENST00000570308.5:c.-349-27490T>C

Variant summary

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

The ENST00000570308.5(MMP2):​c.-349-27490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,176 control chromosomes in the GnomAD database, including 51,917 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 0.82 (51917 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 2 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-AS1 (HGNC:53142): (MMP2 antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2-AS1	NR_147198.1	n.406+7051A>G		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-349-27490T>C		intron_variant	Intron 1 of 13	1		ENSP00000461421.1
MMP2-AS1	ENST00000565307.1	n.247+7051A>G		intron_variant	Intron 2 of 2	4
MMP2-AS1	ENST00000569037.5	n.406+7051A>G		intron_variant	Intron 4 of 5	5
MMP2-AS1	ENST00000789013.1	n.286+7051A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124097 AN: 152058 Hom.: 51891 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.816 AC: 124171 AN: 152176 Hom.: 51917 Cov.: 33 AF XY: 0.819 AC XY: 60968 AN XY: 74404

African (AFR) AF: 0.611 AC: 25348 AN: 41480

American (AMR) AF: 0.902 AC: 13789 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3468

East Asian (EAS) AF: 0.917 AC: 4742 AN: 5174

South Asian (SAS) AF: 0.858 AC: 4136 AN: 4822

European-Finnish (FIN) AF: 0.914 AC: 9701 AN: 10608

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60709 AN: 68018

Other (OTH) AF: 0.852 AC: 1801 AN: 2114

Alfa AF: 0.869 Hom.: 31066

Bravo AF: 0.807

Asia WGS AF: 0.870 AC: 3026 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	3.0
DANN	Benign	0.74
PhyloP100		-0.74
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: rs2576561; hg19: chr16-55470974;