chr16-55477894-C-T

Variant names:

• chr16-55477894-C-T
• rs243865
• ENST00000570308.5:c.-75-5015C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -1.93

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]

ACMG classification

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-75-5015C>T		intron_variant	Intron 2 of 13	1		ENSP00000461421.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28505 AN: 152036 Hom.: 3258 Cov.: 32

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

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

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

Jan 01, 2016

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Significance: association

Review Status: criteria provided, single submitter

Collection Method: case-control

The 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

Other links and lift over

dbSNP: rs243865; hg19: chr16-55511806;