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rs2241145

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004530.6(MMP2):c.833-255G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 528,814 control chromosomes in the GnomAD database, including 56,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 16436 hom., cov: 33)
Exomes 𝑓: 0.46 ( 40341 hom. )

Consequence

MMP2
NM_004530.6 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 16-55488288-G-C is Benign according to our data. Variant chr16-55488288-G-C is described in ClinVar as [Benign]. Clinvar id is 1280447.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MMP2NM_004530.6 linkuse as main transcriptc.833-255G>C intron_variant ENST00000219070.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP2ENST00000219070.9 linkuse as main transcriptc.833-255G>C intron_variant 1 NM_004530.6 P1P08253-1
ENST00000623886.1 linkuse as main transcriptn.1671G>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.465
AC:
70683
AN:
151994
Hom.:
16403
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.481
Gnomad AMI
AF:
0.568
Gnomad AMR
AF:
0.504
Gnomad ASJ
AF:
0.411
Gnomad EAS
AF:
0.489
Gnomad SAS
AF:
0.507
Gnomad FIN
AF:
0.418
Gnomad MID
AF:
0.446
Gnomad NFE
AF:
0.450
Gnomad OTH
AF:
0.472
GnomAD4 exome
AF:
0.459
AC:
173033
AN:
376702
Hom.:
40341
Cov.:
3
AF XY:
0.462
AC XY:
92019
AN XY:
199336
show subpopulations
Gnomad4 AFR exome
AF:
0.477
Gnomad4 AMR exome
AF:
0.514
Gnomad4 ASJ exome
AF:
0.397
Gnomad4 EAS exome
AF:
0.501
Gnomad4 SAS exome
AF:
0.512
Gnomad4 FIN exome
AF:
0.420
Gnomad4 NFE exome
AF:
0.447
Gnomad4 OTH exome
AF:
0.453
GnomAD4 genome
AF:
0.465
AC:
70756
AN:
152112
Hom.:
16436
Cov.:
33
AF XY:
0.466
AC XY:
34643
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.481
Gnomad4 AMR
AF:
0.504
Gnomad4 ASJ
AF:
0.411
Gnomad4 EAS
AF:
0.489
Gnomad4 SAS
AF:
0.507
Gnomad4 FIN
AF:
0.418
Gnomad4 NFE
AF:
0.450
Gnomad4 OTH
AF:
0.476
Alfa
AF:
0.459
Hom.:
2047
Bravo
AF:
0.472
Asia WGS
AF:
0.521
AC:
1814
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.055
Dann
Benign
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2241145; hg19: chr16-55522200; COSMIC: COSV54602148; COSMIC: COSV54602148; API