rs145997165

Variant names:

• chr15-41505054-C-T
• rs145997165
• NM_002344.6:c.1936G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002344.6(LTK):​c.1936G>A​(p.Ala646Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,612,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 7 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 35 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	NM_002344.6	MANE Select	c.1936G>A	p.Ala646Thr	missense	Exon 16 of 20	NP_002335.2
	LTK	NM_206961.4		c.1753G>A	p.Ala585Thr	missense	Exon 15 of 19	NP_996844.1	P29376-4
	LTK	NM_001135685.2		c.1546G>A	p.Ala516Thr	missense	Exon 14 of 18	NP_001129157.1	P29376-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	ENST00000263800.11	TSL:1 MANE Select	c.1936G>A	p.Ala646Thr	missense	Exon 16 of 20	ENSP00000263800.6	P29376-1
	LTK	ENST00000355166.9	TSL:1	c.1753G>A	p.Ala585Thr	missense	Exon 15 of 19	ENSP00000347293.5	P29376-4
	LTK	ENST00000561619.5	TSL:1	c.1030G>A	p.Ala344Thr	missense	Exon 10 of 14	ENSP00000458111.1	H3BVG6

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152078 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000208 AC: 52 AN: 249428 AF XY: 0.000185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000308 AC: 450 AN: 1460500 Hom.: 0 Cov.: 32 AF XY: 0.000299 AC XY: 217 AN XY: 726524

African (AFR) AF: 0.0000299 AC: 1 AN: 33422

American (AMR) AF: 0.0000225 AC: 1 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86136

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000367 AC: 408 AN: 1111314

Other (OTH) AF: 0.000232 AC: 14 AN: 60334

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74414

African (AFR) AF: 0.000217 AC: 9 AN: 41524

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000291 Hom.: 0

Bravo AF: 0.000242

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	0.85	L
PhyloP100		2.6
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.75
MVP		0.83
MPC		0.54
ClinPred		0.26	T
GERP RS		2.6
Varity_R		0.40
gMVP		0.26
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs145997165; hg19: chr15-41797252; COSMIC: COSV53027033; COSMIC: COSV53027033;