Variant 17-78925053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003255.5(TIMP2):c.36C>T(p.Leu12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,184,470 control chromosomes in the GnomAD database, including 726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.024 ( 74 hom., cov: 29)

Exomes 𝑓: 0.034 ( 652 hom. )

Consequence

TIMP2
NM_003255.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.612

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-78925053-G-A is Benign according to our data. Variant chr17-78925053-G-A is described in ClinVar as [Benign]. Clinvar id is 3038074.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.612 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0243 (3589/147722) while in subpopulation NFE AF= 0.0359 (2388/66532). AF 95% confidence interval is 0.0347. There are 74 homozygotes in gnomad4. There are 1844 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 74 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMP2	NM_003255.5 linkuse as main transcript	c.36C>T	p.Leu12=	synonymous_variant	1/5	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.36C>T	p.Leu12=	synonymous_variant	1/5	1	NM_003255.5	ENSP00000262768	P1

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3590

AN:

147618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00566

Gnomad AMI

AF:

0.00561

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0560

AC:

434

AN:

7754

Hom.:

AF XY:

0.0578

AC XY:

295

AN XY:

5104

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0312

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0571

Gnomad FIN exome

AF:

0.0885

Gnomad NFE exome

AF:

0.0539

Gnomad OTH exome

AF:

0.0556

GnomAD4 exome

AF:

0.0340

AC:

35288

AN:

1036748

Hom.:

652

Cov.:

AF XY:

0.0343

AC XY:

16915

AN XY:

493266

show subpopulations

Gnomad4 AFR exome

AF:

0.00411

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.000139

Gnomad4 SAS exome

AF:

0.0335

Gnomad4 FIN exome

AF:

0.0537

Gnomad4 NFE exome

AF:

0.0358

Gnomad4 OTH exome

AF:

0.0298

GnomAD4 genome

AF:

0.0243

AC:

3589

AN:

147722

Hom.:

Cov.:

AF XY:

0.0256

AC XY:

1844

AN XY:

72052

show subpopulations

Gnomad4 AFR

AF:

0.00565

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.0574

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0288

Hom.:

Bravo

AF:

0.0198

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

Oct 21, 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

-0.68

CADD

Benign

DANN

Benign

0.92

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