15-41504014-A-C

Variant names:

• chr15-41504014-A-C
• NM_002344.6:c.2577T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002344.6(LTK):​c.2577T>G​(p.Asn859Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.508

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2788021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTK	NM_002344.6	c.2577T>G	p.Asn859Lys	missense_variant	Exon 20 of 20	ENST00000263800.11	NP_002335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTK	ENST00000263800.11	c.2577T>G	p.Asn859Lys	missense_variant	Exon 20 of 20	1	NM_002344.6	ENSP00000263800.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2577T>G (p.N859K) alteration is located in exon 20 (coding exon 20) of the LTK gene. This alteration results from a T to G substitution at nucleotide position 2577, causing the asparagine (N) at amino acid position 859 to be replaced by a lysine (K). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;T;.
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.4	.;M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.32
MutPred		0.29		.;Gain of methylation at N859 (P = 0.0042);.;.;
MVP		0.70
MPC		0.58
ClinPred		0.98	D
GERP RS		0.40
Varity_R		0.21
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41796212;