15-41504154-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_002344.6(LTK):c.2437G>T(p.Glu813Ter) 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, single submitter B:1
• Conservation: PhyloP100: 0.293

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 Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_002344.6 Downstream stopcodon found after 82 codons.
• 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 id is 789531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 612 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTK	NM_002344.6	c.2437G>T	p.Glu813Ter	stop_gained	20/20	ENST00000263800.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTK	ENST00000263800.11	c.2437G>T	p.Glu813Ter	stop_gained	20/20	1	NM_002344.6	P2

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

GnomAD3 exomes AF: 0.00379 AC: 948 AN: 250032 Hom.: 2 AF XY: 0.00375 AC XY: 508 AN XY: 135310

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 SAS exome AF: 0.000784

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

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.00700

Gnomad4 NFE exome AF: 0.00561

Gnomad4 OTH exome AF: 0.00419

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

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00537

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00389 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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D;D;D;D
Vest4		0.41
GERP RS		0.71

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