chr16-55485789-C-T

Variant names:

• chr16-55485789-C-T
• rs17859889
• NM_004530.6:c.832+12C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004530.6(MMP2):​c.832+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,611,964 control chromosomes in the GnomAD database, including 1,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (108 hom., cov: 32)
  • Exomes 𝑓: 0.025 (918 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0370

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-55485789-C-T is Benign according to our data. Variant chr16-55485789-C-T is described in ClinVar as [Benign]. Clinvar id is 319752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-55485789-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.832+12C>T		intron_variant	Intron 5 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.832+12C>T		intron_variant	Intron 5 of 12	1	NM_004530.6	ENSP00000219070.4

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4568 AN: 152088 Hom.: 109 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0359

GnomAD3 exomes AF: 0.0405 AC: 10093 AN: 249428 Hom.: 305 AF XY: 0.0412 AC XY: 5563 AN XY: 135000

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.0487

Gnomad ASJ exome AF: 0.0473

Gnomad EAS exome AF: 0.0977

Gnomad SAS exome AF: 0.0735

Gnomad FIN exome AF: 0.0478

Gnomad NFE exome AF: 0.0205

Gnomad OTH exome AF: 0.0345

GnomAD4 exome AF: 0.0255 AC: 37197 AN: 1459758 Hom.: 918 Cov.: 34 AF XY: 0.0271 AC XY: 19704 AN XY: 726188

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0455

Gnomad4 EAS exome AF: 0.0863

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0301 AC: 4575 AN: 152206 Hom.: 108 Cov.: 32 AF XY: 0.0330 AC XY: 2455 AN XY: 74410

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0780

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0258 Hom.: 13

Bravo AF: 0.0280

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Multicentric osteolysis nodulosis arthropathy spectrum Benign:1

Jan 13, 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	-0.86
CADD	Benign	0.40
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs17859889; hg19: chr16-55519701; COSMIC: COSV54605002; COSMIC: COSV54605002;