rs857403

Positions:

• chr16-55482796-T-A
• chr16-55482796-T-C
• chr16-55482796-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004530.6(MMP2):​c.154-113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 918,598 control chromosomes in the GnomAD database, including 304,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46501 hom., cov: 32)
  • Exomes 𝑓: 0.82 (257921 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-55482796-T-A is Benign according to our data. Variant chr16-55482796-T-A is described in ClinVar as [Benign]. Clinvar id is 1223276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.154-113T>A		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.154-113T>A		intron_variant		1	NM_004530.6	P1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118503 AN: 152006 Hom.: 46472 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.819 AC: 627824 AN: 766474 Hom.: 257921 AF XY: 0.821 AC XY: 328325 AN XY: 400138

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.838

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.834

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.780 AC: 118586 AN: 152124 Hom.: 46501 Cov.: 32 AF XY: 0.781 AC XY: 58056 AN XY: 74370

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.757

Alfa AF: 0.812 Hom.: 5917

Bravo AF: 0.771

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs857403; hg19: chr16-55516708;