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rs243865

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000570308.5(MMP2):c.-75-5015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,156 control chromosomes in the GnomAD database, including 3,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

Frequency

Genomes: 𝑓 0.19 ( 3255 hom., cov: 32)

Consequence

MMP2
ENST00000570308.5 intron

Scores

2

Clinical Significance

association criteria provided, single submitter O:1

Conservation

PhyloP100: -1.93
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP2ENST00000570308.5 linkuse as main transcriptc.-75-5015C>T intron_variant 1 P08253-2

Frequencies

GnomAD3 genomes
AF:
0.187
AC:
28505
AN:
152036
Hom.:
3258
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0643
Gnomad AMI
AF:
0.241
Gnomad AMR
AF:
0.212
Gnomad ASJ
AF:
0.198
Gnomad EAS
AF:
0.105
Gnomad SAS
AF:
0.151
Gnomad FIN
AF:
0.290
Gnomad MID
AF:
0.190
Gnomad NFE
AF:
0.249
Gnomad OTH
AF:
0.183
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.187
AC:
28505
AN:
152156
Hom.:
3255
Cov.:
32
AF XY:
0.189
AC XY:
14021
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0643
Gnomad4 AMR
AF:
0.212
Gnomad4 ASJ
AF:
0.198
Gnomad4 EAS
AF:
0.105
Gnomad4 SAS
AF:
0.151
Gnomad4 FIN
AF:
0.290
Gnomad4 NFE
AF:
0.249
Gnomad4 OTH
AF:
0.180
Alfa
AF:
0.201
Hom.:
938
Bravo
AF:
0.174
Asia WGS
AF:
0.123
AC:
426
AN:
3478

ClinVar

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

Submissions by phenotype

Lip and oral cavity carcinoma Other:1
association, criteria provided, single submittercase-controlDepartment of Biological Science, Sunandan Divatia School of Science, NMIMS UniversityJan 01, 2016The heterozygous (CT) genotype showed a higher frequency in cases as compared to controls and a significant association was observed with an OR of 1.469 (1.13-1.90). The homozygous WT (CC) genotype indicated decreased risk to oral cancer with an OR 0.669 (0.51-0.86) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.30
Dann
Benign
0.84

Splicing

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: rs243865; hg19: chr16-55511806; API