17-78863834-C-A

Position:

• chr17-78863834-C-A

Variant summary

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

The NM_003255.5(TIMP2):​c.341-6188G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,116 control chromosomes in the GnomAD database, including 2,031 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 0.16 (2031 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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]

LOC124904068 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMP2	NM_003255.5	c.341-6188G>T		intron_variant		ENST00000262768.11
LOC124904068	XR_007065924.1	n.203+1407C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMP2	ENST00000262768.11	c.341-6188G>T		intron_variant		1	NM_003255.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23762 AN: 151998 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.156 AC: 23772 AN: 152116 Hom.: 2031 Cov.: 32 AF XY: 0.154 AC XY: 11467 AN XY: 74376

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.155

Alfa AF: 0.106 Hom.: 226

Bravo AF: 0.160

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.27

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: rs9905930; hg19: chr17-76859916;