chr17-78925057-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003255.5(TIMP2):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000063 in 1,110,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

TIMP2
NM_003255.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.080179065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5 link	c.32C>T	p.Ala11Val	missense_variant	Exon 1 of 5	ENST00000262768.11	NP_003246.1	P16035A0A140VK57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11 link	c.32C>T	p.Ala11Val	missense_variant	Exon 1 of 5	1	NM_003255.5	ENSP00000262768.6		P16035

Frequencies

GnomAD3 genomes

AF:

0.0000144

AC:

AN:

139004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000703

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000206

AC:

AN:

4846

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00242

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000515

AC:

AN:

971444

Hom.:

Cov.:

AF XY:

0.00000872

AC XY:

AN XY:

458522

show subpopulations

African (AFR)

AF:

0.0000518

AC:

AN:

19320

American (AMR)

AF:

0.000189

AC:

AN:

5278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10228

East Asian (EAS)

AF:

0.00

AC:

AN:

16922

South Asian (SAS)

AF:

0.0000859

AC:

AN:

23290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

846020

Other (OTH)

AF:

0.0000281

AC:

AN:

35554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000144

AC:

AN:

139004

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

67256

show subpopulations

African (AFR)

AF:

0.0000255

AC:

AN:

39168

American (AMR)

AF:

0.0000703

AC:

AN:

14220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

4116

South Asian (SAS)

AF:

0.00

AC:

AN:

3974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63652

Other (OTH)

AF:

0.00

AC:

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.32C>T (p.A11V) alteration is located in exon 1 (coding exon 1) of the TIMP2 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the alanine (A) at amino acid position 11 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.55

PhyloP100

1.5

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Benign

0.20

Sift4G

Benign

0.51

Polyphen

0.0010

Vest4

0.24

MutPred

0.35

Loss of disorder (P = 0.038);

MVP

0.15

MPC

0.68

ClinPred

0.038

GERP RS

1.2

PromoterAI

-0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.091

gMVP

0.38

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr17-78925057-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over