rs1420228

Positions:

• chr16-55451261-G-A
• chr16-55451261-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570308.5(MMP2):​c.-349-13291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,170 control chromosomes in the GnomAD database, including 52,749 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 0.82 (52749 hom., cov: 31)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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-AS1 (HGNC:53142): (MMP2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP2-AS1	NR_147198.1	n.212+1511C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP2	ENST00000570308.5	c.-349-13291G>A		intron_variant		1
MMP2-AS1	ENST00000569037.5	n.212+1511C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125320 AN: 152052 Hom.: 52718 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.824 AC: 125392 AN: 152170 Hom.: 52749 Cov.: 31 AF XY: 0.829 AC XY: 61705 AN XY: 74400

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.851

Alfa AF: 0.871 Hom.: 77389

Bravo AF: 0.816

Asia WGS AF: 0.930 AC: 3233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1420228; hg19: chr16-55485173;