rs243836

Positions:

• chr16-55500324-G-A
• chr16-55500324-G-T

Variant summary

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

The NM_004530.6(MMP2):​c.1769+1876G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,734 control chromosomes in the GnomAD database, including 16,607 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 0.46 (16607 hom., cov: 31)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.1769+1876G>A		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.1769+1876G>A		intron_variant		1	NM_004530.6	P1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70413 AN: 151616 Hom.: 16605 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.464 AC: 70436 AN: 151734 Hom.: 16607 Cov.: 31 AF XY: 0.467 AC XY: 34615 AN XY: 74132

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.454

Alfa AF: 0.455 Hom.: 7948

Bravo AF: 0.449

Asia WGS AF: 0.519 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.45
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs243836; hg19: chr16-55534236;