rs567092201

Variant names:

• chr16-55479277-TGCGGCGGCGGCGGCG-T
• rs567092201
• NM_004530.6:c.-195_-181delCGGCGGCGGCGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr16-55479277-TGCGGCGGCGGCGGCG-T
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCGGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCGGCGGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCGGCGGCGGCGGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCGGCGGCGGCGGCGGCG
• chr16-55479277-TGCGGCGGCGGCGGCG-TGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004530.6(MMP2):​c.-195_-181delCGGCGGCGGCGGCGG variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000498 in 401,290 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: MMP2 NM_004530.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP2	NM_004530.6	c.-195_-181delCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 13	ENST00000219070.9	NP_004521.1
MMP2	NM_001302508.1	c.-76+320_-76+334delCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 12		NP_001289437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP2	ENST00000219070.9	c.-195_-181delCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 13	1	NM_004530.6	ENSP00000219070.4
MMP2	ENST00000570308.5	c.-75-3624_-75-3610delCGGCGGCGGCGGCGG		intron_variant	Intron 2 of 13	1		ENSP00000461421.1
MMP2	ENST00000568715.5	c.-76+320_-76+334delCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 3	4		ENSP00000457949.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151274 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000400 AC: 1 AN: 250016 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126948

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5860

American (AMR) AF: 0.00 AC: 0 AN: 5234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6518

East Asian (EAS) AF: 0.00 AC: 0 AN: 16292

South Asian (SAS) AF: 0.00 AC: 0 AN: 4122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1082

European-Non Finnish (NFE) AF: 0.00000557 AC: 1 AN: 179684

Other (OTH) AF: 0.00 AC: 0 AN: 13866

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151274 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73868

African (AFR) AF: 0.00 AC: 0 AN: 41250

American (AMR) AF: 0.00 AC: 0 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67734

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

Splicing

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

Other links and lift over

dbSNP: rs567092201; hg19: chr16-55513189;