rs2241146

Variant names:

• chr16-55488322-G-A
• rs2241146
• NM_004530.6:c.833-221G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55488322-G-A
• chr16-55488322-G-C
• chr16-55488322-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• multicentric osteolysis, nodulosis, and arthropathy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000279030 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1256667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.833-221G>A		intron_variant	Intron 5 of 12	ENST00000219070.9	NP_004521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.833-221G>A		intron_variant	Intron 5 of 12	1	NM_004530.6	ENSP00000219070.4

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

African (AFR) AF: 0.0771 AC: 935 AN: 12128

American (AMR) AF: 0.0953 AC: 1856 AN: 19478

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 577 AN: 13078

East Asian (EAS) AF: 0.179 AC: 5117 AN: 28634

South Asian (SAS) AF: 0.126 AC: 5811 AN: 46122

European-Finnish (FIN) AF: 0.0494 AC: 1296 AN: 26220

Middle Eastern (MID) AF: 0.0670 AC: 123 AN: 1836

European-Non Finnish (NFE) AF: 0.0198 AC: 5050 AN: 255030

Other (OTH) AF: 0.0447 AC: 1098 AN: 24544

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

African (AFR) AF: 0.0779 AC: 3236 AN: 41534

American (AMR) AF: 0.0690 AC: 1055 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.195 AC: 1007 AN: 5164

South Asian (SAS) AF: 0.130 AC: 625 AN: 4824

European-Finnish (FIN) AF: 0.0477 AC: 507 AN: 10622

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0212 AC: 1444 AN: 68022

Other (OTH) AF: 0.0592 AC: 125 AN: 2112

Alfa AF: 0.0358 Hom.: 335

Bravo AF: 0.0569

Asia WGS AF: 0.149 AC: 521 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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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
PhyloP100		-1.2
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241146; hg19: chr16-55522234;