rs2305030

chr15-41513039-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002344.6(LTK):c.125G>A(p.Arg42Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,612,268 control chromosomes in the GnomAD database, including 12,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.12 (1262 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11098 hom.)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011280775).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTK	NM_002344.6	c.125G>A	p.Arg42Gln	missense_variant	2/20	ENST00000263800.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTK	ENST00000263800.11	c.125G>A	p.Arg42Gln	missense_variant	2/20	1	NM_002344.6	P2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17770 AN: 152074 Hom.: 1261 Cov.: 33

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.131 AC: 32211 AN: 245754 Hom.: 2823 AF XY: 0.127 AC XY: 17075 AN XY: 134044

Gnomad AFR exome AF: 0.0946

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.0572

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.0960

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.117 AC: 170518 AN: 1460076 Hom.: 11098 Cov.: 36 AF XY: 0.116 AC XY: 84115 AN XY: 726390

Gnomad4 AFR exome AF: 0.0941

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0550

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.117 AC: 17779 AN: 152192 Hom.: 1262 Cov.: 33 AF XY: 0.119 AC XY: 8841 AN XY: 74382

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.113

Alfa AF: 0.109 Hom.: 2192

Bravo AF: 0.118

TwinsUK AF: 0.107 AC: 398

ALSPAC AF: 0.111 AC: 429

ESP6500AA AF: 0.0921 AC: 405

ESP6500EA AF: 0.107 AC: 917

ExAC AF: 0.127 AC: 15344

Asia WGS AF: 0.218 AC: 759 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	2.0
Dann	Benign	0.92
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.52	T;T;T
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.60	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.38	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.054
MPC		0.13
ClinPred		0.00028	T
GERP RS		-6.4
Varity_R		0.023
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs2305030; hg19: chr15-41805237; COSMIC: COSV55489955; COSMIC: COSV55489955;