Variant rs34764696 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK7	NM_002821.5 linkuse as main transcript	c.2330C>T	p.Ala777Val	missense_variant	15/20	ENST00000230419.9	NP_002812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK7	ENST00000230419.9 linkuse as main transcript	c.2330C>T	p.Ala777Val	missense_variant	15/20	1	NM_002821.5	ENSP00000230419	P1	Q13308-1

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

GnomAD3 exomes

AF:

0.0468

AC:

11762

AN:

251360

Hom.:

343

AF XY:

0.0486

AC XY:

6599

AN XY:

135864

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 SAS exome

AF:

0.0422

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

Gnomad4 AFR exome

AF:

0.0456

Gnomad4 AMR exome

AF:

0.0242

Gnomad4 ASJ exome

AF:

0.0228

Gnomad4 EAS exome

AF:

0.00912

Gnomad4 SAS exome

AF:

0.0430

Gnomad4 FIN exome

AF:

0.0485

Gnomad4 NFE exome

AF:

0.0739

Gnomad4 OTH exome

AF:

0.0565

GnomAD4 genome

AF:

0.0540

AC:

8223

AN:

152304

Hom.:

239

Cov.:

AF XY:

0.0520

AC XY:

3870

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0476

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00809

Gnomad4 SAS

AF:

0.0392

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0693

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0628

Hom.:

510

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTK7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

T;.;.;.;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.84

T;T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.81

L;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.11

T;T;T;D;T;D

Sift4G

Uncertain

0.0080

D;D;D;D;D;D

Polyphen

0.15

B;B;B;B;.;.

Vest4

0.21

MPC

0.25

ClinPred

0.011

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.22

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