chr16-55493770-A-G

Variant names:

• chr16-55493770-A-G
• rs183112
• NM_004530.6:c.1472+477A>G

Variant summary

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

The NM_004530.6(MMP2):​c.1472+477A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,198 control chromosomes in the GnomAD database, including 48,195 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 0.79 (48195 hom., cov: 33)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	NM_004530.6	MANE Select	c.1472+477A>G		intron	N/A	NP_004521.1
	MMP2	NM_001127891.3		c.1322+477A>G		intron	N/A	NP_001121363.1
	MMP2	NM_001302508.1		c.1244+477A>G		intron	N/A	NP_001289437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000219070.9	TSL:1 MANE Select	c.1472+477A>G		intron	N/A	ENSP00000219070.4
	MMP2	ENST00000437642.6	TSL:1	c.1322+477A>G		intron	N/A	ENSP00000394237.2
	MMP2	ENST00000570308.5	TSL:1	c.1244+477A>G		intron	N/A	ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120338 AN: 152080 Hom.: 48168 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.791 AC: 120416 AN: 152198 Hom.: 48195 Cov.: 33 AF XY: 0.796 AC XY: 59230 AN XY: 74416

African (AFR) AF: 0.660 AC: 27353 AN: 41464

American (AMR) AF: 0.806 AC: 12335 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2906 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4073 AN: 5170

South Asian (SAS) AF: 0.887 AC: 4290 AN: 4834

European-Finnish (FIN) AF: 0.876 AC: 9300 AN: 10614

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57508 AN: 68028

Other (OTH) AF: 0.780 AC: 1648 AN: 2114

Alfa AF: 0.829 Hom.: 96623

Bravo AF: 0.780

Asia WGS AF: 0.831 AC: 2884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.29
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: rs183112; hg19: chr16-55527682;