rs776833403

Variant names:

• chr15-41504555-C-G
• rs776833403
• NM_002344.6:c.2206G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-41504555-C-G
• chr15-41504555-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002344.6(LTK):​c.2206G>C​(p.Val736Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V736I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LTK NM_002344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3804655).
• BS2: High AC in GnomAdExome4 at 6 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.2206G>C	p.Val736Leu	missense	Exon 18 of 20	NP_002335.2
	LTK	NM_206961.4		c.2023G>C	p.Val675Leu	missense	Exon 17 of 19	NP_996844.1	P29376-4
	LTK	NM_001135685.2		c.1816G>C	p.Val606Leu	missense	Exon 16 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.2206G>C	p.Val736Leu	missense	Exon 18 of 20	ENSP00000263800.6	P29376-1
	LTK	ENST00000355166.9	TSL:1	c.2023G>C	p.Val675Leu	missense	Exon 17 of 19	ENSP00000347293.5	P29376-4
	LTK	ENST00000561619.5	TSL:1	c.1300G>C	p.Val434Leu	missense	Exon 12 of 14	ENSP00000458111.1	H3BVG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461554 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111972

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	0.0028	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.62	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.57	N
PhyloP100		1.3
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.16	T
Polyphen		0.66	P
Vest4		0.52
MutPred		0.57		Gain of methylation at R741 (P = 0.1558)
MVP		0.52
MPC		0.13
ClinPred		0.33	T
GERP RS		-0.51
Varity_R		0.48
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs776833403; hg19: chr15-41796753;