Variant 6-43076969-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002821.5(PTK7):c.79+402C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,508,026 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 19 hom. )

Consequence

PTK7
NM_002821.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.206

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041211247).

BP6

Variant 6-43076969-C-A is Benign according to our data. Variant chr6-43076969-C-A is described in ClinVar as [Benign]. Clinvar id is 3050084.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 582 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK7	NM_002821.5 linkuse as main transcript	c.79+402C>A		intron_variant		ENST00000230419.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK7	ENST00000230419.9 linkuse as main transcript	c.79+402C>A		intron_variant		1	NM_002821.5	P1	Q13308-1

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

582

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00570

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00333

AC:

414

AN:

124278

Hom.:

AF XY:

0.00363

AC XY:

247

AN XY:

68096

show subpopulations

Gnomad AFR exome

AF:

0.000501

Gnomad AMR exome

AF:

0.000866

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00148

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00485

AC:

6574

AN:

1355670

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3138

AN XY:

665256

show subpopulations

Gnomad4 AFR exome

AF:

0.000618

Gnomad4 AMR exome

AF:

0.000916

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.00547

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00382

AC:

582

AN:

152356

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00570

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00313

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ExAC

AF:

0.00161

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PTK7-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

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

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.9

DANN

Benign

0.95

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.13

REVEL

Benign

0.11

Sift

Uncertain

0.029

Sift4G

Benign

0.061

Vest4

0.18

MVP

0.18

MPC

0.41

ClinPred

0.016

GERP RS

1.6

gMVP

0.14

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