rs243842

Variant names:

• chr16-55493510-T-C
• rs243842
• NM_004530.6:c.1472+217T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-55493510-T-C
• chr16-55493510-T-A

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.1472+217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,062 control chromosomes in the GnomAD database, including 10,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10141 hom., cov: 32)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.167
• Publications: 25 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-55493510-T-C is Benign according to our data. Variant chr16-55493510-T-C is described in ClinVar as Benign. ClinVar VariationId is 1245813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 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.1472+217T>C		intron	N/A	NP_004521.1	P08253-1
	MMP2	NM_001127891.3		c.1322+217T>C		intron	N/A	NP_001121363.1	P08253-3
	MMP2	NM_001302508.1		c.1244+217T>C		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.1472+217T>C		intron	N/A	ENSP00000219070.4	P08253-1
	MMP2	ENST00000437642.6	TSL:1	c.1322+217T>C		intron	N/A	ENSP00000394237.2	P08253-3
	MMP2	ENST00000570308.5	TSL:1	c.1244+217T>C		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55354 AN: 151944 Hom.: 10137 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.364 AC: 55371 AN: 152062 Hom.: 10141 Cov.: 32 AF XY: 0.367 AC XY: 27297 AN XY: 74316

African (AFR) AF: 0.331 AC: 13709 AN: 41468

American (AMR) AF: 0.315 AC: 4818 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1538 AN: 5170

South Asian (SAS) AF: 0.388 AC: 1869 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4731 AN: 10556

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26074 AN: 67978

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.378 Hom.: 18995

Bravo AF: 0.353

Asia WGS AF: 0.316 AC: 1096 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		-0.17
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: rs243842; hg19: chr16-55527422;