Variant chr15-41505944-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002344.6(LTK):c.1603G>A(p.Asp535Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0256 in 1,613,806 control chromosomes in the GnomAD database, including 647 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 50 hom., cov: 33)

Exomes 𝑓: 0.026 ( 597 hom. )

Consequence

LTK
NM_002344.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

LTK (HGNC:6721): (leukocyte receptor tyrosine kinase) The protein encoded by this gene is a member of the ros/insulin receptor family of tyrosine kinases. Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

LTK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005242139).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0189 (2879/152280) while in subpopulation SAS AF= 0.0356 (172/4830). AF 95% confidence interval is 0.0313. There are 50 homozygotes in gnomad4. There are 1383 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2879 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTK	NM_002344.6 linkuse as main transcript	c.1603G>A	p.Asp535Asn	missense_variant	12/20	ENST00000263800.11	NP_002335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTK	ENST00000263800.11 linkuse as main transcript	c.1603G>A	p.Asp535Asn	missense_variant	12/20	1	NM_002344.6	ENSP00000263800	P2	P29376-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2883

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0222

AC:

5581

AN:

251258

Hom.:

AF XY:

0.0236

AC XY:

3206

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.00984

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.00729

Gnomad SAS exome

AF:

0.0338

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0263

AC:

38489

AN:

1461526

Hom.:

597

Cov.:

AF XY:

0.0267

AC XY:

19406

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0431

Gnomad4 EAS exome

AF:

0.00355

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0189

AC:

2879

AN:

152280

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1383

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00529

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0378

Gnomad4 EAS

AF:

0.00580

Gnomad4 SAS

AF:

0.0356

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0278

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.0181

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0270

AC:

104

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.0295

AC:

254

ExAC

AF:

0.0228

AC:

2770

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0261

EpiControl

AF:

0.0274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

.;T;D

Eigen

Benign

0.095

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.86

.;L;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.051

T;D;D

Polyphen

0.83

P;P;.

Vest4

0.16

MPC

0.12

ClinPred

0.056

GERP RS

0.83

Varity_R

0.44

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over