chr15-41505944-C-T

Variant names:

• chr15-41505944-C-T
• rs35932273
• NM_002344.6:c.1603G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002344.6(LTK):​c.1603G>A​(p.Asp535Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0256 in 1,613,806 control chromosomes in the GnomAD database, including 647 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.019 (50 hom., cov: 33)
  • Exomes 𝑓: 0.026 (597 hom.)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94
• Publications: 20 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=0.005242139).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0189 (2879/152280) while in subpopulation SAS AF = 0.0356 (172/4830). AF 95% confidence interval is 0.0313. There are 50 homozygotes in GnomAd4. There are 1383 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2879 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	NM_002344.6	MANE Select	c.1603G>A	p.Asp535Asn	missense	Exon 12 of 20	NP_002335.2
	LTK	NM_206961.4		c.1420G>A	p.Asp474Asn	missense	Exon 11 of 19	NP_996844.1
	LTK	NM_001135685.2		c.1243-167G>A		intron	N/A	NP_001129157.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTK	ENST00000263800.11	TSL:1 MANE Select	c.1603G>A	p.Asp535Asn	missense	Exon 12 of 20	ENSP00000263800.6
	LTK	ENST00000355166.9	TSL:1	c.1420G>A	p.Asp474Asn	missense	Exon 11 of 19	ENSP00000347293.5
	LTK	ENST00000561619.5	TSL:1	c.697G>A	p.Asp233Asn	missense	Exon 6 of 14	ENSP00000458111.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2883 AN: 152162 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0222 AC: 5581 AN: 251258 AF XY: 0.0236

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.00984

Gnomad ASJ exome AF: 0.0411

Gnomad EAS exome AF: 0.00729

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0225

GnomAD4 exome AF: 0.0263 AC: 38489 AN: 1461526 Hom.: 597 Cov.: 31 AF XY: 0.0267 AC XY: 19406 AN XY: 727090

African (AFR) AF: 0.00397 AC: 133 AN: 33478

American (AMR) AF: 0.0102 AC: 455 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 1127 AN: 26122

East Asian (EAS) AF: 0.00355 AC: 141 AN: 39696

South Asian (SAS) AF: 0.0337 AC: 2908 AN: 86226

European-Finnish (FIN) AF: 0.0119 AC: 635 AN: 53380

Middle Eastern (MID) AF: 0.0302 AC: 174 AN: 5768

European-Non Finnish (NFE) AF: 0.0284 AC: 31562 AN: 1111762

Other (OTH) AF: 0.0224 AC: 1354 AN: 60388

GnomAD4 genome AF: 0.0189 AC: 2879 AN: 152280 Hom.: 50 Cov.: 33 AF XY: 0.0186 AC XY: 1383 AN XY: 74460

African (AFR) AF: 0.00529 AC: 220 AN: 41552

American (AMR) AF: 0.0171 AC: 261 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.00580 AC: 30 AN: 5176

South Asian (SAS) AF: 0.0356 AC: 172 AN: 4830

European-Finnish (FIN) AF: 0.0108 AC: 115 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0278 AC: 1891 AN: 68016

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0236 Hom.: 31

Bravo AF: 0.0181

TwinsUK AF: 0.0297 AC: 110

ALSPAC AF: 0.0270 AC: 104

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0295 AC: 254

ExAC AF: 0.0228 AC: 2770

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.86	L
PhyloP100		3.9
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.051	T
Polyphen		0.83	P
Vest4		0.16
MPC		0.12
ClinPred		0.056	T
GERP RS		0.83
Varity_R		0.44
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs35932273; hg19: chr15-41798142; COSMIC: COSV53027141; COSMIC: COSV53027141;