rs34764696

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002821.5(PTK7):c.2330C>T(p.Ala777Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,614,106 control chromosomes in the GnomAD database, including 3,649 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.054 ( 239 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3410 hom. )

Consequence

PTK7
NM_002821.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.19

Publications

26 publications found

Variant links:

Genes affected

PTK7 (HGNC:9618): (protein tyrosine kinase 7 (inactive)) This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

PTK7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002228111).

BP6

Variant 6-43144529-C-T is Benign according to our data. Variant chr6-43144529-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060982.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002821.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTK7	NM_002821.5	MANE Select	c.2330C>T	p.Ala777Val	missense	Exon 15 of 20	NP_002812.2
PTK7	NM_001270398.2		c.2354C>T	p.Ala785Val	missense	Exon 15 of 20	NP_001257327.1	Q13308-6
PTK7	NM_152880.4		c.2210C>T	p.Ala737Val	missense	Exon 14 of 19	NP_690619.1	Q13308-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTK7	ENST00000230419.9	TSL:1 MANE Select	c.2330C>T	p.Ala777Val	missense	Exon 15 of 20	ENSP00000230419.4	Q13308-1
PTK7	ENST00000345201.6	TSL:1	c.2210C>T	p.Ala737Val	missense	Exon 14 of 19	ENSP00000325992.4	Q13308-2
PTK7	ENST00000352931.6	TSL:1	c.2162C>T	p.Ala721Val	missense	Exon 14 of 19	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8205

AN:

152186

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00807

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0693

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0468

AC:

11762

AN:

251360

AF XY:

0.0486

show subpopulations

Gnomad AFR exome

AF:

0.0437

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.00620

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0648

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0654

AC:

95608

AN:

1461802

Hom.:

3410

Cov.:

AF XY:

0.0647

AC XY:

47055

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0456

AC:

1528

AN:

33480

American (AMR)

AF:

0.0242

AC:

1080

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

597

AN:

26134

East Asian (EAS)

AF:

0.00912

AC:

362

AN:

39698

South Asian (SAS)

AF:

0.0430

AC:

3710

AN:

86252

European-Finnish (FIN)

AF:

0.0485

AC:

2591

AN:

53390

Middle Eastern (MID)

AF:

0.0186

AC:

107

AN:

5768

European-Non Finnish (NFE)

AF:

0.0739

AC:

82222

AN:

1111970

Other (OTH)

AF:

0.0565

AC:

3411

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5585

11170

16754

22339

27924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3048

6096

9144

12192

15240

<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:

0.0540

AC:

8223

AN:

152304

Hom.:

239

Cov.:

AF XY:

0.0520

AC XY:

3870

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0476

AC:

1980

AN:

41564

American (AMR)

AF:

0.0361

AC:

552

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3472

East Asian (EAS)

AF:

0.00809

AC:

AN:

5190

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4822

European-Finnish (FIN)

AF:

0.0455

AC:

483

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0693

AC:

4712

AN:

68008

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

400

800

1199

1599

1999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0627

Hom.:

982

Bravo

AF:

0.0532

TwinsUK

AF:

0.0742

AC:

275

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.0433

AC:

191

ESP6500EA

AF:

0.0702

AC:

604

ExAC

AF:

0.0477

AC:

5789

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0645

EpiControl

AF:

0.0597

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PTK7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.81

PhyloP100

2.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Uncertain

0.0080

Polyphen

0.15

Vest4

0.21

MPC

0.25

ClinPred

0.011

GERP RS

3.7

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.22

Mutation Taster

=95/5

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over