rs243832

chr16-55505279-C-Gchr16-55505279-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004530.6(MMP2):c.1880-60C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,403,922 control chromosomes in the GnomAD database, including 175,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19226 hom., cov: 31)
  • Exomes 𝑓: 0.50 (155808 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.105

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-55505279-C-G is Benign according to our data. Variant chr16-55505279-C-G is described in ClinVar as [Benign]. Clinvar id is 1234221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.1880-60C>G		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.1880-60C>G		intron_variant		1	NM_004530.6	P1
MMP2	ENST00000437642.6	c.1730-60C>G		intron_variant		1
MMP2	ENST00000570308.5	c.1652-60C>G		intron_variant		1
MMP2	ENST00000543485.5	c.1652-60C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76271 AN: 151782 Hom.: 19219 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.497 AC: 622035 AN: 1252022 Hom.: 155808 AF XY: 0.496 AC XY: 314722 AN XY: 633954

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.502 AC: 76303 AN: 151900 Hom.: 19226 Cov.: 31 AF XY: 0.506 AC XY: 37539 AN XY: 74222

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.478

Alfa AF: 0.482 Hom.: 2167

Bravo AF: 0.496

Asia WGS AF: 0.565 AC: 1969 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.7
Dann	Benign	0.64

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: rs243832; hg19: chr16-55539191; COSMIC: COSV50894590; COSMIC: COSV50894590;