rs2252070

Variant names:

• chr11-102955810-C-T
• rs2252070
• NM_002427.4:c.-105G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002427.4(MMP13):​c.-105G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,529,566 control chromosomes in the GnomAD database, including 343,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34448 hom., cov: 32)
  • Exomes 𝑓: 0.67 (309071 hom.)
• Consequence: MMP13 NM_002427.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.38
• Publications: 115 publications found

Genes affected

MMP13 (HGNC:7159): (matrix metallopeptidase 13) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MMP13 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia, Missouri type

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• metaphyseal chondrodysplasia, Spahr type

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• metaphyseal anadysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-102955810-C-T is Benign according to our data. Variant chr11-102955810-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP13	NM_002427.4	c.-105G>A		upstream_gene_variant		ENST00000260302.8	NP_002418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP13	ENST00000260302.8	c.-105G>A		upstream_gene_variant		1	NM_002427.4	ENSP00000260302.3
MMP13	ENST00000340273.4	c.-105G>A		upstream_gene_variant		1		ENSP00000339672.4

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101897 AN: 151950 Hom.: 34424 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.668 AC: 919882 AN: 1377498 Hom.: 309071 AF XY: 0.665 AC XY: 457185 AN XY: 687902

African (AFR) AF: 0.724 AC: 23042 AN: 31838

American (AMR) AF: 0.653 AC: 28413 AN: 43508

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 14841 AN: 25440

East Asian (EAS) AF: 0.469 AC: 18333 AN: 39116

South Asian (SAS) AF: 0.602 AC: 50092 AN: 83200

European-Finnish (FIN) AF: 0.628 AC: 29688 AN: 47250

Middle Eastern (MID) AF: 0.596 AC: 2403 AN: 4032

European-Non Finnish (NFE) AF: 0.684 AC: 715620 AN: 1045698

Other (OTH) AF: 0.652 AC: 37450 AN: 57416

GnomAD4 genome AF: 0.671 AC: 101978 AN: 152068 Hom.: 34448 Cov.: 32 AF XY: 0.662 AC XY: 49207 AN XY: 74318

African (AFR) AF: 0.717 AC: 29726 AN: 41468

American (AMR) AF: 0.652 AC: 9970 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2412 AN: 5160

South Asian (SAS) AF: 0.605 AC: 2918 AN: 4822

European-Finnish (FIN) AF: 0.604 AC: 6395 AN: 10586

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46316 AN: 67964

Other (OTH) AF: 0.657 AC: 1388 AN: 2112

Alfa AF: 0.687 Hom.: 10553

Bravo AF: 0.675

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27245877, 26635116, 12392760, 18308831) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		1.4
PromoterAI		0.053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2252070; hg19: chr11-102826539; COSMIC: COSV52823914;