rs243845

Variant names:

• chr16-55492575-G-A
• rs243845
• NM_004530.6:c.1337-583G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55492575-G-A
• chr16-55492575-G-C
• chr16-55492575-G-T

Variant summary

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

The NM_004530.6(MMP2):​c.1337-583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,470 control chromosomes in the GnomAD database, including 11,564 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 0.39 (11564 hom., cov: 29)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 19 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	NM_004530.6	MANE Select	c.1337-583G>A		intron	N/A	NP_004521.1	P08253-1
	MMP2	NM_001127891.3		c.1187-583G>A		intron	N/A	NP_001121363.1	P08253-3
	MMP2	NM_001302508.1		c.1109-583G>A		intron	N/A	NP_001289437.1	P08253-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000219070.9	TSL:1 MANE Select	c.1337-583G>A		intron	N/A	ENSP00000219070.4	P08253-1
	MMP2	ENST00000437642.6	TSL:1	c.1187-583G>A		intron	N/A	ENSP00000394237.2	P08253-3
	MMP2	ENST00000570308.5	TSL:1	c.1109-583G>A		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58952 AN: 151352 Hom.: 11559 Cov.: 29

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.389 AC: 58984 AN: 151470 Hom.: 11564 Cov.: 29 AF XY: 0.392 AC XY: 28979 AN XY: 74006

African (AFR) AF: 0.421 AC: 17331 AN: 41186

American (AMR) AF: 0.322 AC: 4897 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1583 AN: 3460

East Asian (EAS) AF: 0.284 AC: 1465 AN: 5156

South Asian (SAS) AF: 0.387 AC: 1855 AN: 4790

European-Finnish (FIN) AF: 0.449 AC: 4691 AN: 10458

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26076 AN: 67904

Other (OTH) AF: 0.350 AC: 735 AN: 2098

Alfa AF: 0.386 Hom.: 16607

Bravo AF: 0.382

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs243845; hg19: chr16-55526487;