rs2425019

Variant names:

• chr20-35231612-A-G
• rs2425019
• NM_006690.4:c.246+4628A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006690.4(MMP24):​c.246+4628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,086 control chromosomes in the GnomAD database, including 28,538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (28538 hom., cov: 32)
• Consequence: MMP24 NM_006690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 28 publications found

Genes affected

MMP24 (HGNC:7172): (matrix metallopeptidase 24) 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. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]

MMP24-AS1-EDEM2 (HGNC:):

MMP24OS (HGNC:44421): (MMP24 opposite strand)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24	NM_006690.4	c.246+4628A>G		intron_variant	Intron 1 of 8	ENST00000246186.8	NP_006681.1
MMP24-AS1-EDEM2	NM_001355008.2	c.-352+4469T>C		intron_variant	Intron 3 of 14		NP_001341937.1
MMP24	XM_017027597.2	c.246+4628A>G		intron_variant	Intron 1 of 7		XP_016883086.1
MMP24	XM_011528500.3	c.246+4628A>G		intron_variant	Intron 1 of 7		XP_011526802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP24	ENST00000246186.8	c.246+4628A>G		intron_variant	Intron 1 of 8	1	NM_006690.4	ENSP00000246186.6

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87745 AN: 151968 Hom.: 28471 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.547

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87865 AN: 152086 Hom.: 28538 Cov.: 32 AF XY: 0.577 AC XY: 42918 AN XY: 74336

African (AFR) AF: 0.893 AC: 37063 AN: 41486

American (AMR) AF: 0.428 AC: 6532 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1876 AN: 3464

East Asian (EAS) AF: 0.347 AC: 1796 AN: 5174

South Asian (SAS) AF: 0.605 AC: 2920 AN: 4824

European-Finnish (FIN) AF: 0.511 AC: 5394 AN: 10562

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30470 AN: 67984

Other (OTH) AF: 0.552 AC: 1166 AN: 2112

Alfa AF: 0.489 Hom.: 15036

Bravo AF: 0.578

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.67
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2425019; hg19: chr20-33819415;