Variant 15-41504427-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_002344.6(LTK):c.2261G>A(p.Arg754His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

LTK
NM_002344.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.774

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTK	NM_002344.6 linkuse as main transcript	c.2261G>A	p.Arg754His	missense_variant	19/20	ENST00000263800.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTK	ENST00000263800.11 linkuse as main transcript	c.2261G>A	p.Arg754His	missense_variant	19/20	1	NM_002344.6	P2	P29376-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251176

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000602

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.2261G>A (p.R754H) alteration is located in exon 19 (coding exon 19) of the LTK gene. This alteration results from a G to A substitution at nucleotide position 2261, causing the arginine (R) at amino acid position 754 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Benign

0.0086

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Uncertain

-0.0025

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-4.4

D;D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.019

D;D;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.98

D;D;.;.

Vest4

0.49

MutPred

0.51

.;Gain of catalytic residue at M756 (P = 0.1153);.;.;

MVP

0.91

MPC

0.15

ClinPred

0.93

GERP RS

-0.85

Varity_R

0.21

gMVP

0.34

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