15-41505023-G-C

Variant names:

• chr15-41505023-G-C
• NM_002344.6:c.1967C>G

Variant summary

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

The NM_002344.6(LTK):​c.1967C>G​(p.Pro656Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64

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=0.36207056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTK	NM_002344.6	c.1967C>G	p.Pro656Arg	missense_variant	Exon 16 of 20	ENST00000263800.11	NP_002335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTK	ENST00000263800.11	c.1967C>G	p.Pro656Arg	missense_variant	Exon 16 of 20	1	NM_002344.6	ENSP00000263800.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461268 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726910

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	.;T;D;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T;T;T;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.17	.;N;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.4	D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.098	T;T;T;T
Polyphen		0.16	B;P;.;.
Vest4		0.49
MutPred		0.51		.;Gain of MoRF binding (P = 0.0074);.;.;
MVP		0.72
MPC		0.31
ClinPred		0.93	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.16

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: chr15-41797221;