rs243866

Positions:

• chr16-55477625-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570308.5(MMP2):​c.-75-5284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,844 control chromosomes in the GnomAD database, including 3,225 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 0.19 (3225 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000570308.5	c.-75-5284G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28142 AN: 151726 Hom.: 3228 Cov.: 31

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.185 AC: 28136 AN: 151844 Hom.: 3225 Cov.: 31 AF XY: 0.186 AC XY: 13836 AN XY: 74198

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.180

Alfa AF: 0.230 Hom.: 5813

Bravo AF: 0.172

Asia WGS AF: 0.122 AC: 422 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	0.30
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs243866; hg19: chr16-55511537;