rs2241146

chr16-55488322-G-Achr16-55488322-G-Cchr16-55488322-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004530.6(MMP2):c.833-221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 579,316 control chromosomes in the GnomAD database, including 1,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (351 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1220 hom.)
• Consequence: MMP2 NM_004530.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-55488322-G-A is Benign according to our data. Variant chr16-55488322-G-A is described in ClinVar as [Benign]. Clinvar id is 1256667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2	NM_004530.6	c.833-221G>A		intron_variant		ENST00000219070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000219070.9	c.833-221G>A		intron_variant		1	NM_004530.6	P1
	ENST00000623886.1	n.1705G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8177 AN: 152130 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0512 AC: 21863 AN: 427070 Hom.: 1220 Cov.: 4 AF XY: 0.0554 AC XY: 12465 AN XY: 225178

Gnomad4 AFR exome AF: 0.0771

Gnomad4 AMR exome AF: 0.0953

Gnomad4 ASJ exome AF: 0.0441

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0494

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0447

GnomAD4 genome AF: 0.0539 AC: 8200 AN: 152246 Hom.: 351 Cov.: 32 AF XY: 0.0580 AC XY: 4319 AN XY: 74438

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0196 Hom.: 16

Bravo AF: 0.0569

Asia WGS AF: 0.149 AC: 521 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.20
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2241146; hg19: chr16-55522234;