Genetic Variant PTK2:c.2832+227A>G (chr8-140674071-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001352702.2(PTK2):c.2832+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 678,756 control chromosomes in the GnomAD database, including 31,281 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 0.28 ( 6360 hom., cov: 31)

Exomes 𝑓: 0.30 ( 24921 hom. )

Consequence

PTK2
NM_001352702.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.112

Publications

16 publications found

Variant links:

Genes affected

PTK2 (HGNC:9611): (protein tyrosine kinase 2) This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

PTK2 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2	NM_001352702.2 link	c.2832+227A>G		intron_variant	Intron 32 of 35	ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1 link	c.2832+227A>G		intron_variant	Intron 32 of 35		NM_001352702.2	ENSP00000512868.1		A0A8Q3WLM4

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42371

AN:

151784

Hom.:

6350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.298

AC:

157255

AN:

526854

Hom.:

24921

AF XY:

0.298

AC XY:

86278

AN XY:

289700

show subpopulations

African (AFR)

AF:

0.196

AC:

3120

AN:

15928

American (AMR)

AF:

0.406

AC:

16067

AN:

39596

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

6379

AN:

18340

East Asian (EAS)

AF:

0.0856

AC:

2535

AN:

29618

South Asian (SAS)

AF:

0.282

AC:

18672

AN:

66250

European-Finnish (FIN)

AF:

0.311

AC:

8951

AN:

28808

Middle Eastern (MID)

AF:

0.314

AC:

1173

AN:

3736

European-Non Finnish (NFE)

AF:

0.311

AC:

92110

AN:

296482

Other (OTH)

AF:

0.294

AC:

8248

AN:

28096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6328

12656

18983

25311

31639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.279

AC:

42384

AN:

151902

Hom.:

6360

Cov.:

AF XY:

0.279

AC XY:

20732

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.198

AC:

8222

AN:

41434

American (AMR)

AF:

0.394

AC:

6012

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1148

AN:

3466

East Asian (EAS)

AF:

0.0845

AC:

436

AN:

5158

South Asian (SAS)

AF:

0.270

AC:

1301

AN:

4818

European-Finnish (FIN)

AF:

0.292

AC:

3070

AN:

10524

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21290

AN:

67954

Other (OTH)

AF:

0.266

AC:

562

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1504

3008

4511

6015

7519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.309

Hom.:

2946

Bravo

AF:

0.277

Asia WGS

AF:

0.195

AC:

678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.7

(source)

DANN

Benign

0.75

PhyloP100

-0.11

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