rs2241145

chr16-55488288-G-Cchr16-55488288-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.833-255G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 528,814 control chromosomes in the GnomAD database, including 56,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (16436 hom., cov: 33)
  • Exomes 𝑓: 0.46 (40341 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-55488288-G-C is Benign according to our data. Variant chr16-55488288-G-C is described in ClinVar as [Benign]. Clinvar id is 1280447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.833-255G>C		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.833-255G>C		intron_variant		1	NM_004530.6	P1
	ENST00000623886.1	n.1671G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70683 AN: 151994 Hom.: 16403 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.459 AC: 173033 AN: 376702 Hom.: 40341 Cov.: 3 AF XY: 0.462 AC XY: 92019 AN XY: 199336

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.465 AC: 70756 AN: 152112 Hom.: 16436 Cov.: 33 AF XY: 0.466 AC XY: 34643 AN XY: 74352

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.476

Alfa AF: 0.459 Hom.: 2047

Bravo AF: 0.472

Asia WGS AF: 0.521 AC: 1814 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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.47

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: rs2241145; hg19: chr16-55522200; COSMIC: COSV54602148; COSMIC: COSV54602148;