Variant 6-43076902-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002821.5(PTK7):c.79+335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,511,964 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 11 hom., cov: 32)

Exomes 𝑓: 0.010 ( 78 hom. )

Consequence

PTK7
NM_002821.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.879

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003965497).

BP6

Variant 6-43076902-G-A is Benign according to our data. Variant chr6-43076902-G-A is described in ClinVar as [Benign]. Clinvar id is 2656576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK7	NM_002821.5 linkuse as main transcript	c.79+335G>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+335G>A		intron_variant		1	NM_002821.5	P1	Q13308-1

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1363

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00645

AC:

812

AN:

125938

Hom.:

AF XY:

0.00609

AC XY:

421

AN XY:

69122

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.00425

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000514

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0102

AC:

13830

AN:

1359638

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

6679

AN XY:

667530

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00753

Gnomad4 ASJ exome

AF:

0.00485

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000617

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00992

GnomAD4 genome

AF:

0.00895

AC:

1364

AN:

152326

Hom.:

Cov.:

AF XY:

0.00913

AC XY:

680

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00864

Hom.:

Bravo

AF:

0.00860

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00649

AC:

ExAC

AF:

0.00256

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PTK7-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PTK7: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.4

DANN

Benign

0.93

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.24

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Vest4

0.13

MutPred

0.30

Gain of MoRF binding (P = 0.0019);

MVP

0.068

MPC

0.42

ClinPred

0.072

GERP RS

2.4

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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