chr16-55451261-G-A

Variant names:

• chr16-55451261-G-A
• rs1420228
• ENST00000570308.5:c.-349-13291G>A

Variant summary

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

The ENST00000570308.5(MMP2):​c.-349-13291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,170 control chromosomes in the GnomAD database, including 52,749 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 0.82 (52749 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2-AS1	NR_147198.1		n.212+1511C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000570308.5	TSL:1	c.-349-13291G>A		intron	N/A	ENSP00000461421.1
	MMP2-AS1	ENST00000569037.5	TSL:5	n.212+1511C>T		intron	N/A
	MMP2-AS1	ENST00000789013.1		n.93-4313C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125320 AN: 152052 Hom.: 52718 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.824 AC: 125392 AN: 152170 Hom.: 52749 Cov.: 31 AF XY: 0.829 AC XY: 61705 AN XY: 74400

African (AFR) AF: 0.640 AC: 26559 AN: 41484

American (AMR) AF: 0.913 AC: 13959 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2799 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4945 AN: 5176

South Asian (SAS) AF: 0.920 AC: 4433 AN: 4820

European-Finnish (FIN) AF: 0.919 AC: 9756 AN: 10618

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 60007 AN: 68000

Other (OTH) AF: 0.851 AC: 1798 AN: 2112

Alfa AF: 0.851 Hom.: 107755

Bravo AF: 0.816

Asia WGS AF: 0.930 AC: 3233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.78
PhyloP100		-1.2
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: rs1420228; hg19: chr16-55485173;