17-78925357-G-T

Position:

• chr17-78925357-G-T

Variant summary

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

The NM_003255.5(TIMP2):​c.-269C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 152,052 control chromosomes in the GnomAD database, including 113 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 0.018 (109 hom., cov: 32)
  • Exomes 𝑓: 0.083 (4 hom.)
• Consequence: TIMP2 NM_003255.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.-269C>A		5_prime_UTR_variant	1/5	ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11	c.-269C>A		5_prime_UTR_variant	1/5	1	NM_003255.5	ENSP00000262768.6

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2704 AN: 151122 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00289

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.0825 AC: 68 AN: 824 Hom.: 4 Cov.: 0 AF XY: 0.0893 AC XY: 35 AN XY: 392

Gnomad4 SAS exome AF: 0.0838

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0179 AC: 2707 AN: 151228 Hom.: 109 Cov.: 32 AF XY: 0.0210 AC XY: 1551 AN XY: 73852

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00289

Gnomad4 ASJ AF: 0.000872

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.0177

Alfa AF: 0.00253 Hom.: 0

Bravo AF: 0.0156

Asia WGS AF: 0.107 AC: 345 AN: 3232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs7503607; hg19: chr17-76921439;