dbSNP rs7187391: MMP2:c.-349-20004T>C (chr16-55444548-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000570308.5(MMP2):c.-349-20004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,160 control chromosomes in the GnomAD database, including 385 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 0.045 ( 385 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP2
ENST00000570308.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

0 publications found

Variant links:

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 links:

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

MMP2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2-AS1	NR_147198.1 link	n.298-327A>G		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
MMP2	ENST00000570308.5 link	c.-349-20004T>C	intron_variant	Intron 1 of 13	1	ENSP00000461421.1
MMP2-AS1	ENST00000565307.1 link	n.138+74A>G	intron_variant	Intron 1 of 2	4
MMP2-AS1	ENST00000569037.5 link	n.298-327A>G	intron_variant	Intron 3 of 5	5
MMP2-AS1	ENST00000789013.1 link	n.178-327A>G	intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6892

AN:

152044

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00830

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00637

Gnomad OTH

AF:

0.0364

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0453

AC:

6894

AN:

152160

Hom.:

385

Cov.:

AF XY:

0.0446

AC XY:

3315

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.136

AC:

5627

AN:

41500

American (AMR)

AF:

0.0160

AC:

245

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.0430

AC:

222

AN:

5160

South Asian (SAS)

AF:

0.0114

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00830

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00637

AC:

433

AN:

68004

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

311

621

932

1242

1553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0262

Hom.:

299

Bravo

AF:

0.0509

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over