rs2305030

Variant names:

• chr15-41513039-C-T
• rs2305030
• NM_002344.6:c.125G>A

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002344.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	NM_002344.6	MANE Select	c.125G>A	p.Arg42Gln	missense	Exon 2 of 20	NP_002335.2
	LTK	NM_206961.4		c.125G>A	p.Arg42Gln	missense	Exon 2 of 19	NP_996844.1
	LTK	NM_001135685.2		c.125G>A	p.Arg42Gln	missense	Exon 2 of 18	NP_001129157.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	ENST00000263800.11	TSL:1 MANE Select	c.125G>A	p.Arg42Gln	missense	Exon 2 of 20	ENSP00000263800.6
	LTK	ENST00000355166.9	TSL:1	c.125G>A	p.Arg42Gln	missense	Exon 2 of 19	ENSP00000347293.5
	LTK	ENST00000561619.5	TSL:1	c.43+628G>A		intron	N/A	ENSP00000458111.1

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

GnomAD2 exomes AF: 0.131 AC: 32211 AN: 245754 AF XY: 0.127

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 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

African (AFR) AF: 0.0941 AC: 3143 AN: 33390

American (AMR) AF: 0.135 AC: 5991 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 1434 AN: 26084

East Asian (EAS) AF: 0.321 AC: 12735 AN: 39670

South Asian (SAS) AF: 0.100 AC: 8644 AN: 86170

European-Finnish (FIN) AF: 0.125 AC: 6622 AN: 52840

Middle Eastern (MID) AF: 0.0661 AC: 379 AN: 5736

European-Non Finnish (NFE) AF: 0.112 AC: 124115 AN: 1111590

Other (OTH) AF: 0.124 AC: 7455 AN: 60326

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

African (AFR) AF: 0.0945 AC: 3926 AN: 41538

American (AMR) AF: 0.126 AC: 1921 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1904 AN: 5162

South Asian (SAS) AF: 0.105 AC: 507 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1414 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7500 AN: 68006

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.111 Hom.: 3642

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 v4.9

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
DEOGEN2	Benign	0.025	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.0
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.12
Sift	Benign	0.38	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.054
MPC		0.13
ClinPred		0.00028	T
GERP RS		-6.4
Varity_R		0.023
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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