NM_002344.6:c.2437G>T

Variant names:

• chr15-41504154-C-A
• rs148281714
• NM_002344.6:c.2437G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_002344.6(LTK):​c.2437G>T​(p.Glu813*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,978 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (24 hom.)
• Consequence: LTK NM_002344.6 stop_gained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.293
• Publications: 14 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.

• BP6: Variant 15-41504154-C-A is Benign according to our data. Variant chr15-41504154-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 789531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 612 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.2437G>T	p.Glu813*	stop_gained	Exon 20 of 20	NP_002335.2
	LTK	NM_206961.4		c.2254G>T	p.Glu752*	stop_gained	Exon 19 of 19	NP_996844.1	P29376-4
	LTK	NM_001135685.2		c.2047G>T	p.Glu683*	stop_gained	Exon 18 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.2437G>T	p.Glu813*	stop_gained	Exon 20 of 20	ENSP00000263800.6	P29376-1
	LTK	ENST00000355166.9	TSL:1	c.2254G>T	p.Glu752*	stop_gained	Exon 19 of 19	ENSP00000347293.5	P29376-4
	LTK	ENST00000561619.5	TSL:1	c.1531G>T	p.Glu511*	stop_gained	Exon 14 of 14	ENSP00000458111.1	H3BVG6

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 612 AN: 152218 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00536

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00379 AC: 948 AN: 250032 AF XY: 0.00375

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00642

Gnomad NFE exome AF: 0.00568

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00485 AC: 7096 AN: 1461642 Hom.: 24 Cov.: 32 AF XY: 0.00478 AC XY: 3473 AN XY: 727128

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.00304 AC: 136 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86248

European-Finnish (FIN) AF: 0.00700 AC: 373 AN: 53278

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00561 AC: 6234 AN: 1111946

Other (OTH) AF: 0.00419 AC: 253 AN: 60386

GnomAD4 genome AF: 0.00402 AC: 612 AN: 152336 Hom.: 2 Cov.: 33 AF XY: 0.00439 AC XY: 327 AN XY: 74496

African (AFR) AF: 0.00118 AC: 49 AN: 41578

American (AMR) AF: 0.00477 AC: 73 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00772 AC: 82 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00537 AC: 365 AN: 68030

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00388 Hom.: 1

Bravo AF: 0.00354

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00570 AC: 49

ExAC AF: 0.00394 AC: 478

EpiCase AF: 0.00474

EpiControl AF: 0.00539

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Benign	0.96
Eigen	Benign	0.17
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.19	N
PhyloP100		0.29
Vest4		0.41
GERP RS		0.71
Mutation Taster		=159/41	polymorphism

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: rs148281714; hg19: chr15-41796352; COSMIC: COSV53026508; COSMIC: COSV53026508;