chr16-55479032-G-T

Position:

• chr16-55479032-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000570308.5(MMP2):​c.-75-3877G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 142,864 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (306 hom., cov: 31)
  • Exomes 𝑓: 0.038 (2 hom.)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.148

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-55479032-G-T is Benign according to our data. Variant chr16-55479032-G-T is described in ClinVar as [Benign]. Clinvar id is 1280738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_001302508.1	c.-76+67G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000570308.5	c.-75-3877G>T		intron_variant		1
MMP2	ENST00000568715.5	c.-76+67G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8079 AN: 141858 Hom.: 304 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00557

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0733

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0640

GnomAD4 exome AF: 0.0379 AC: 35 AN: 924 Hom.: 2 Cov.: 0 AF XY: 0.0440 AC XY: 24 AN XY: 546

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0357

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0570 AC: 8084 AN: 141940 Hom.: 306 Cov.: 31 AF XY: 0.0585 AC XY: 4004 AN XY: 68492

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.00177

Gnomad4 SAS AF: 0.0595

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.0636

Alfa AF: 0.0370 Hom.: 32

Bravo AF: 0.0498

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs17859829; hg19: chr16-55512944;