Genetic Variant NM_003255.5:c.232-97C>A (chr17-78871103-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003255.5(TIMP2):c.232-97C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 942,062 control chromosomes in the GnomAD database, including 291,771 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 0.76 ( 44152 hom., cov: 31)

Exomes 𝑓: 0.79 ( 247619 hom. )

Consequence

TIMP2
NM_003255.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

11 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5 link	c.232-97C>A		intron_variant	Intron 2 of 4	ENST00000262768.11	NP_003246.1	P16035A0A140VK57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11 link	c.232-97C>A		intron_variant	Intron 2 of 4	1	NM_003255.5	ENSP00000262768.6		P16035

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115046

AN:

151842

Hom.:

44139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.776

GnomAD4 exome

AF:

0.787

AC:

621570

AN:

790102

Hom.:

247619

AF XY:

0.780

AC XY:

318693

AN XY:

408454

show subpopulations

African (AFR)

AF:

0.671

AC:

13128

AN:

19570

American (AMR)

AF:

0.854

AC:

28172

AN:

32976

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

15094

AN:

17746

East Asian (EAS)

AF:

0.580

AC:

19771

AN:

34108

South Asian (SAS)

AF:

0.590

AC:

34984

AN:

59328

European-Finnish (FIN)

AF:

0.821

AC:

38438

AN:

46802

Middle Eastern (MID)

AF:

0.780

AC:

3213

AN:

4118

European-Non Finnish (NFE)

AF:

0.817

AC:

439856

AN:

538194

Other (OTH)

AF:

0.776

AC:

28914

AN:

37260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

5936

11872

17808

23744

29680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7084

14168

21252

28336

35420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.757

AC:

115100

AN:

151960

Hom.:

44152

Cov.:

AF XY:

0.756

AC XY:

56154

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.672

AC:

27854

AN:

41428

American (AMR)

AF:

0.812

AC:

12379

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

2938

AN:

3472

East Asian (EAS)

AF:

0.545

AC:

2812

AN:

5160

South Asian (SAS)

AF:

0.561

AC:

2703

AN:

4816

European-Finnish (FIN)

AF:

0.819

AC:

8641

AN:

10556

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55289

AN:

67962

Other (OTH)

AF:

0.771

AC:

1626

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1382

2764

4147

5529

6911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.755

Hom.:

2732

Bravo

AF:

0.754

Asia WGS

AF:

0.585

AC:

2031

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

(source)

DANN

Benign

0.61

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over