rs2236307

Variant names:

• chr14-22843714-T-C
• rs2236307
• NM_004995.4:c.855T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-22843714-T-C
• chr14-22843714-T-A
• chr14-22843714-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004995.4(MMP14):​c.855T>C​(p.Gly285Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,585,932 control chromosomes in the GnomAD database, including 38,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4628 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33646 hom.)
• Consequence: MMP14 NM_004995.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.841
• Publications: 26 publications found

Genes affected

MMP14 (HGNC:7160): (matrix metallopeptidase 14) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

MMP14 Gene-Disease associations (from GenCC):

• Winchester syndrome

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-22843714-T-C is Benign according to our data. Variant chr14-22843714-T-C is described in ClinVar as Benign. ClinVar VariationId is 1177852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.841 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004995.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	NM_004995.4	MANE Select	c.855T>C	p.Gly285Gly	synonymous	Exon 6 of 10	NP_004986.1	P50281

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	ENST00000311852.11	TSL:1 MANE Select	c.855T>C	p.Gly285Gly	synonymous	Exon 6 of 10	ENSP00000308208.6	P50281
	MMP14	ENST00000928197.1		c.669T>C	p.Gly223Gly	synonymous	Exon 6 of 10	ENSP00000598256.1
	MMP14	ENST00000548162.2	TSL:5	c.855T>C	p.Gly285Gly	synonymous	Exon 6 of 10	ENSP00000506068.1	A0A7P0TAG0

Frequencies

GnomAD3 genomes AF: 0.238 AC: 35999 AN: 151342 Hom.: 4609 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.252

GnomAD2 exomes AF: 0.217 AC: 48562 AN: 224188 AF XY: 0.216

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.212 AC: 304378 AN: 1434474 Hom.: 33646 Cov.: 34 AF XY: 0.212 AC XY: 151448 AN XY: 713424

African (AFR) AF: 0.316 AC: 9921 AN: 31354

American (AMR) AF: 0.137 AC: 4850 AN: 35324

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 4868 AN: 24756

East Asian (EAS) AF: 0.385 AC: 15149 AN: 39364

South Asian (SAS) AF: 0.224 AC: 18414 AN: 82056

European-Finnish (FIN) AF: 0.163 AC: 8667 AN: 53168

Middle Eastern (MID) AF: 0.249 AC: 1405 AN: 5642

European-Non Finnish (NFE) AF: 0.206 AC: 227886 AN: 1103632

Other (OTH) AF: 0.223 AC: 13218 AN: 59178

GnomAD4 genome AF: 0.238 AC: 36058 AN: 151458 Hom.: 4628 Cov.: 31 AF XY: 0.236 AC XY: 17496 AN XY: 74010

African (AFR) AF: 0.310 AC: 12776 AN: 41208

American (AMR) AF: 0.203 AC: 3093 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1919 AN: 5098

South Asian (SAS) AF: 0.231 AC: 1102 AN: 4778

European-Finnish (FIN) AF: 0.161 AC: 1693 AN: 10530

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13972 AN: 67864

Other (OTH) AF: 0.257 AC: 539 AN: 2094

Alfa AF: 0.216 Hom.: 4206

Bravo AF: 0.245

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	MMP14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.60
PhyloP100		0.84
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: rs2236307; hg19: chr14-23312923; COSMIC: COSV61287808; COSMIC: COSV61287808;