rs7201

Variant names:

• chr16-55505702-A-C
• rs7201
• NM_004530.6:c.*260A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-55505702-A-C
• chr16-55505702-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004530.6(MMP2):​c.*260A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 543,508 control chromosomes in the GnomAD database, including 45,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11221 hom., cov: 32)
  • Exomes 𝑓: 0.41 (34745 hom.)
• Consequence: MMP2 NM_004530.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.245
• Publications: 59 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-55505702-A-C is Benign according to our data. Variant chr16-55505702-A-C is described in ClinVar as Benign. ClinVar VariationId is 319776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.*260A>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.*260A>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55890 AN: 151826 Hom.: 11216 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.413 AC: 161820 AN: 391564 Hom.: 34745 Cov.: 1 AF XY: 0.409 AC XY: 84517 AN XY: 206612

African (AFR) AF: 0.200 AC: 2203 AN: 10998

American (AMR) AF: 0.432 AC: 7286 AN: 16866

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 4629 AN: 11754

East Asian (EAS) AF: 0.245 AC: 6468 AN: 26368

South Asian (SAS) AF: 0.341 AC: 14808 AN: 43452

European-Finnish (FIN) AF: 0.409 AC: 10340 AN: 25288

Middle Eastern (MID) AF: 0.420 AC: 699 AN: 1664

European-Non Finnish (NFE) AF: 0.456 AC: 106261 AN: 232824

Other (OTH) AF: 0.408 AC: 9126 AN: 22350

GnomAD4 genome AF: 0.368 AC: 55911 AN: 151944 Hom.: 11221 Cov.: 32 AF XY: 0.364 AC XY: 27063 AN XY: 74258

African (AFR) AF: 0.199 AC: 8255 AN: 41452

American (AMR) AF: 0.442 AC: 6758 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1189 AN: 5144

South Asian (SAS) AF: 0.320 AC: 1536 AN: 4798

European-Finnish (FIN) AF: 0.399 AC: 4216 AN: 10558

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31033 AN: 67924

Other (OTH) AF: 0.391 AC: 826 AN: 2112

Alfa AF: 0.427 Hom.: 56171

Bravo AF: 0.365

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23364396) -

Multicentric osteolysis nodulosis arthropathy spectrum Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		0.24
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: rs7201; hg19: chr16-55539614; COSMIC: COSV50900244; COSMIC: COSV50900244;