rs2576561

Positions:

• chr16-55437062-T-C

Variant summary

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

The ENST00000570308.5(MMP2):​c.-349-27490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,176 control chromosomes in the GnomAD database, including 51,917 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 (51917 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP2-AS1	NR_147198.1	n.406+7051A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000570308.5	c.-349-27490T>C		intron_variant		1		ENSP00000461421
MMP2-AS1	ENST00000569037.5	n.406+7051A>G		intron_variant, non_coding_transcript_variant		5
MMP2-AS1	ENST00000565307.1	n.247+7051A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124097 AN: 152058 Hom.: 51891 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.816 AC: 124171 AN: 152176 Hom.: 51917 Cov.: 33 AF XY: 0.819 AC XY: 60968 AN XY: 74404

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.852

Alfa AF: 0.870 Hom.: 27891

Bravo AF: 0.807

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2576561; hg19: chr16-55470974;