rs865094

Positions:

• chr16-55483320-G-A
• chr16-55483320-G-C

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+185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,150 control chromosomes in the GnomAD database, including 44,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44973 hom., cov: 33)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.716

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=-0.9).
• BP6: Variant 16-55483320-G-A is Benign according to our data. Variant chr16-55483320-G-A is described in ClinVar as [Benign]. Clinvar id is 1226528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.380+185G>A		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.380+185G>A		intron_variant		1	NM_004530.6	P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116316 AN: 152032 Hom.: 44947 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.744

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.765 AC: 116390 AN: 152150 Hom.: 44973 Cov.: 33 AF XY: 0.766 AC XY: 57003 AN XY: 74374

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.745

Alfa AF: 0.812 Hom.: 86184

Bravo AF: 0.755

Asia WGS AF: 0.749 AC: 2604 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	-0.90
CADD	Benign	0.27
DANN	Benign	0.24

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: rs865094; hg19: chr16-55517232;