rs2003241

chr17-78889035-T-C

Variant summary

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

The NM_003255.5(TIMP2):c.131-15116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,114 control chromosomes in the GnomAD database, including 9,128 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 0.25 (9128 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

Genes affected

TIMP2 (HGNC:11821): (TIMP metallopeptidase inhibitor 2) This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMP2	NM_003255.5	c.131-15116A>G		intron_variant		ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMP2	ENST00000262768.11	c.131-15116A>G		intron_variant		1	NM_003255.5	P1
TIMP2	ENST00000536189.6	c.-101-15116A>G		intron_variant		2
TIMP2	ENST00000586713.6	c.-102+11934A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37876 AN: 151996 Hom.: 9098 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.250 AC: 37962 AN: 152114 Hom.: 9128 Cov.: 32 AF XY: 0.246 AC XY: 18312 AN XY: 74372

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.219

Alfa AF: 0.115 Hom.: 2403

Bravo AF: 0.272

Asia WGS AF: 0.241 AC: 843 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	4.8
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2003241; hg19: chr17-76885117;