Genetic Variant NM_002821.5:c.79+402C>T (chr6-43076969-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002821.5(PTK7):c.79+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000637 in 1,508,036 control chromosomes in the GnomAD database, including 1 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 1 hom. )

Consequence

PTK7
NM_002821.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

5 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:

KLC4-AS1 (HGNC:55228): (KLC4 antisense RNA 1)

KLC4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0091480315).

BS2

High AC in GnomAd4 at 10 AD gene.

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.79+402C>T		intron	N/A	NP_002812.2
PTK7	NM_001270398.2		c.86C>T	p.Pro29Leu	missense	Exon 1 of 20	NP_001257327.1	Q13308-6
PTK7	NM_152880.4		c.79+402C>T		intron	N/A	NP_690619.1	Q13308-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTK7	ENST00000230419.9	TSL:1 MANE Select	c.79+402C>T	intron	N/A	ENSP00000230419.4	Q13308-1
PTK7	ENST00000345201.6	TSL:1	c.79+402C>T	intron	N/A	ENSP00000325992.4	Q13308-2
PTK7	ENST00000352931.6	TSL:1	c.79+402C>T	intron	N/A	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000282

AC:

AN:

124278

AF XY:

0.000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00374

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000634

AC:

AN:

1355680

Hom.:

Cov.:

AF XY:

0.0000722

AC XY:

AN XY:

665260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30746

American (AMR)

AF:

0.00

AC:

AN:

33844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24616

East Asian (EAS)

AF:

0.00244

AC:

AN:

34372

South Asian (SAS)

AF:

0.00

AC:

AN:

76950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33440

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059712

Other (OTH)

AF:

0.0000177

AC:

AN:

56390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000656

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000121

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.7

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0091

MetaSVM

Benign

-1.0

PhyloP100

-0.21

PrimateAI

Benign

0.33

PROVEAN

Benign

1.0

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.12

MutPred

0.35

Loss of catalytic residue at P28 (P = 0.0116)

MVP

0.18

MPC

0.36

ClinPred

0.059

GERP RS

1.6

PromoterAI

0.025

Neutral

(source)

gMVP

0.099

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over