rs9302667

Variant names:

• chr16-55422923-A-C
• rs9302667
• ENST00000570308.5:c.-350+32888A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-55422923-A-C
• chr16-55422923-A-G

Variant summary

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

The ENST00000570308.5(MMP2):​c.-350+32888A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,132 control chromosomes in the GnomAD database, including 9,760 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 0.35 (9760 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-350+32888A>C		intron_variant	Intron 1 of 13	1		ENSP00000461421.1
MMP2-AS1	ENST00000789013.1	n.286+21190T>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53692 AN: 152014 Hom.: 9750 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.353 AC: 53750 AN: 152132 Hom.: 9760 Cov.: 33 AF XY: 0.351 AC XY: 26149 AN XY: 74396

African (AFR) AF: 0.432 AC: 17945 AN: 41498

American (AMR) AF: 0.291 AC: 4454 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2257 AN: 5146

South Asian (SAS) AF: 0.392 AC: 1895 AN: 4832

European-Finnish (FIN) AF: 0.308 AC: 3270 AN: 10606

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21928 AN: 67982

Other (OTH) AF: 0.354 AC: 746 AN: 2106

Alfa AF: 0.333 Hom.: 6780

Bravo AF: 0.353

Asia WGS AF: 0.452 AC: 1573 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.66
PhyloP100		-2.3
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: rs9302667; hg19: chr16-55456835;