16-55483250-A-G

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.380+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 769,062 control chromosomes in the GnomAD database, including 50,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10604 hom., cov: 32)
  • Exomes 𝑓: 0.36 (39696 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507

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=-0.93).
• BP6: Variant 16-55483250-A-G is Benign according to our data. Variant chr16-55483250-A-G is described in ClinVar as [Benign]. Clinvar id is 1266020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.380+115A>G		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.380+115A>G		intron_variant		1	NM_004530.6	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56740 AN: 151898 Hom.: 10579 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.356 AC: 219527 AN: 617046 Hom.: 39696 AF XY: 0.354 AC XY: 113056 AN XY: 319412

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.349

GnomAD4 genome AF: 0.374 AC: 56800 AN: 152016 Hom.: 10604 Cov.: 32 AF XY: 0.371 AC XY: 27547 AN XY: 74292

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.367

Alfa AF: 0.367 Hom.: 11083

Bravo AF: 0.384

Asia WGS AF: 0.270 AC: 944 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	-0.93
Cadd	Benign	1.5
Dann	Benign	0.70

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: rs1477017; hg19: chr16-55517162;