Variant chr17-78870935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_003255.5(TIMP2):c.303G>A(p.Ser101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,611,508 control chromosomes in the GnomAD database, including 13,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1205 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12637 hom. )

Consequence

TIMP2
NM_003255.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.10

Variant links:

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]

TIMP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 17-78870935-C-T is Benign according to our data. Variant chr17-78870935-C-T is described in ClinVar as [Benign]. Clinvar id is 3059644.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMP2	NM_003255.5 linkuse as main transcript	c.303G>A	p.Ser101=	synonymous_variant	3/5	ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11 linkuse as main transcript	c.303G>A	p.Ser101=	synonymous_variant	3/5	1	NM_003255.5	ENSP00000262768	P1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17850

AN:

152102

Hom.:

1208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.133

AC:

33339

AN:

249848

Hom.:

2663

AF XY:

0.138

AC XY:

18651

AN XY:

134966

show subpopulations

Gnomad AFR exome

AF:

0.0923

Gnomad AMR exome

AF:

0.0874

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.126

AC:

184176

AN:

1459288

Hom.:

12637

Cov.:

AF XY:

0.129

AC XY:

93521

AN XY:

725800

show subpopulations

Gnomad4 AFR exome

AF:

0.0953

Gnomad4 AMR exome

AF:

0.0910

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.117

AC:

17851

AN:

152220

Hom.:

1205

Cov.:

AF XY:

0.118

AC XY:

8794

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0946

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.115

Hom.:

1332

Bravo

AF:

0.115

Asia WGS

AF:

0.203

AC:

707

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TIMP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

7.8

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over