rs12599775

Positions:

• chr16-55489870-G-C
• chr16-55489870-G-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.1180+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,601,162 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (116 hom., cov: 33)
  • Exomes 𝑓: 0.015 (504 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.14

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=-0.91).
• BP6: Variant 16-55489870-G-C is Benign according to our data. Variant chr16-55489870-G-C is described in ClinVar as [Benign]. Clinvar id is 1248285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.1180+46G>C		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.1180+46G>C		intron_variant		1	NM_004530.6	P1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4482 AN: 152098 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.00715

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00770

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.0314 AC: 7196 AN: 229068 Hom.: 216 AF XY: 0.0298 AC XY: 3694 AN XY: 124114

Gnomad AFR exome AF: 0.0599

Gnomad AMR exome AF: 0.0636

Gnomad ASJ exome AF: 0.0396

Gnomad EAS exome AF: 0.0982

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.00769

Gnomad NFE exome AF: 0.00726

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0149 AC: 21580 AN: 1448946 Hom.: 504 Cov.: 32 AF XY: 0.0155 AC XY: 11167 AN XY: 720316

Gnomad4 AFR exome AF: 0.0585

Gnomad4 AMR exome AF: 0.0619

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.0942

Gnomad4 SAS exome AF: 0.0404

Gnomad4 FIN exome AF: 0.00699

Gnomad4 NFE exome AF: 0.00638

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0295 AC: 4488 AN: 152216 Hom.: 116 Cov.: 33 AF XY: 0.0301 AC XY: 2236 AN XY: 74402

Gnomad4 AFR AF: 0.0565

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.0434

Gnomad4 FIN AF: 0.00715

Gnomad4 NFE AF: 0.00771

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0221 Hom.: 11

Bravo AF: 0.0346

Asia WGS AF: 0.0580 AC: 202 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	-0.91
CADD	Benign	0.017
DANN	Benign	0.48

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: rs12599775; hg19: chr16-55523782;