rs10521323

Positions:

• chr16-55447309-G-A

Variant summary

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

The ENST00000570308.5(MMP2):​c.-349-17243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,134 control chromosomes in the GnomAD database, including 3,824 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 0.21 (3824 hom., cov: 34)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2-AS1	NR_147198.1	n.213-361C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000570308.5	c.-349-17243G>A		intron_variant		1
MMP2-AS1	ENST00000569037.5	n.213-361C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32644 AN: 152016 Hom.: 3830 Cov.: 34

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.00985

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.215 AC: 32640 AN: 152134 Hom.: 3824 Cov.: 34 AF XY: 0.210 AC XY: 15630 AN XY: 74368

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.00988

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.237

Alfa AF: 0.254 Hom.: 7683

Bravo AF: 0.208

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521323; hg19: chr16-55481221;