16-55491248-C-T

Variant names:

• chr16-55491248-C-T
• rs12923011
• NM_004530.6:c.1181-553C>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.1181-553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,864 control chromosomes in the GnomAD database, including 6,783 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 0.27 (6783 hom., cov: 31)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.365 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.1181-553C>T		intron	N/A	NP_004521.1	P08253-1
	MMP2	NM_001127891.3		c.1031-553C>T		intron	N/A	NP_001121363.1	P08253-3
	MMP2	NM_001302508.1		c.953-553C>T		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.1181-553C>T		intron	N/A	ENSP00000219070.4	P08253-1
	MMP2	ENST00000437642.6	TSL:1	c.1031-553C>T		intron	N/A	ENSP00000394237.2	P08253-3
	MMP2	ENST00000570308.5	TSL:1	c.953-553C>T		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41222 AN: 151746 Hom.: 6780 Cov.: 31

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.271 AC: 41216 AN: 151864 Hom.: 6783 Cov.: 31 AF XY: 0.269 AC XY: 19948 AN XY: 74226

African (AFR) AF: 0.0791 AC: 3281 AN: 41472

American (AMR) AF: 0.364 AC: 5554 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3468

East Asian (EAS) AF: 0.145 AC: 747 AN: 5156

South Asian (SAS) AF: 0.250 AC: 1198 AN: 4798

European-Finnish (FIN) AF: 0.320 AC: 3371 AN: 10518

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25020 AN: 67906

Other (OTH) AF: 0.278 AC: 584 AN: 2098

Alfa AF: 0.311 Hom.: 1012

Bravo AF: 0.266

Asia WGS AF: 0.181 AC: 630 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	2.5
DANN	Benign	0.60
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12923011; hg19: chr16-55525160;