chr16-55490086-T-C

Variant names:

• chr16-55490086-T-C
• rs243847
• NM_004530.6:c.1180+262T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004530.6(MMP2):​c.1180+262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,948 control chromosomes in the GnomAD database, including 10,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10355 hom., cov: 32)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.244
• Publications: 28 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-55490086-T-C is Benign according to our data. Variant chr16-55490086-T-C is described in ClinVar as Benign. ClinVar VariationId is 1250038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.1180+262T>C		intron_variant	Intron 7 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.1180+262T>C		intron_variant	Intron 7 of 12	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54732 AN: 151830 Hom.: 10349 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.360 AC: 54748 AN: 151948 Hom.: 10355 Cov.: 32 AF XY: 0.367 AC XY: 27258 AN XY: 74252

African (AFR) AF: 0.233 AC: 9643 AN: 41460

American (AMR) AF: 0.338 AC: 5164 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2051 AN: 5114

South Asian (SAS) AF: 0.467 AC: 2245 AN: 4810

European-Finnish (FIN) AF: 0.498 AC: 5252 AN: 10552

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27810 AN: 67942

Other (OTH) AF: 0.342 AC: 722 AN: 2114

Alfa AF: 0.366 Hom.: 1623

Bravo AF: 0.342

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.56
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs243847; hg19: chr16-55523998;