ENST00000570308.5:c.-349-12170C>T

Variant names:

• chr16-55452382-C-T
• rs837529
• ENST00000570308.5:c.-349-12170C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570308.5(MMP2):​c.-349-12170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,004 control chromosomes in the GnomAD database, including 25,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25151 hom., cov: 32)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 3 publications found

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]

MMP2-AS1 (HGNC:53142): (MMP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2-AS1	NR_147198.1	n.212+390G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-349-12170C>T		intron_variant	Intron 1 of 13	1		ENSP00000461421.1
MMP2-AS1	ENST00000569037.5	n.212+390G>A		intron_variant	Intron 2 of 5	5
MMP2-AS1	ENST00000789013.1	n.93-5434G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85437 AN: 151882 Hom.: 25129 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.562 AC: 85498 AN: 152004 Hom.: 25151 Cov.: 32 AF XY: 0.568 AC XY: 42163 AN XY: 74292

African (AFR) AF: 0.382 AC: 15847 AN: 41440

American (AMR) AF: 0.610 AC: 9314 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2081 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3568 AN: 5152

South Asian (SAS) AF: 0.604 AC: 2906 AN: 4814

European-Finnish (FIN) AF: 0.717 AC: 7568 AN: 10562

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42029 AN: 67980

Other (OTH) AF: 0.600 AC: 1263 AN: 2106

Alfa AF: 0.573 Hom.: 3338

Bravo AF: 0.551

Asia WGS AF: 0.651 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.58
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs837529; hg19: chr16-55486294;