NM_014916.4:c.484G>C

Variant names:

• chr7-98154791-G-C
• rs751573329
• NM_014916.4:c.484G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014916.4(LMTK2):​c.484G>C​(p.Val162Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. V162I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMTK2 NM_014916.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• Publications: 0 publications found

Genes affected

LMTK2 (HGNC:17880): (lemur tyrosine kinase 2) The protein encoded by this gene belongs to the protein kinase superfamily and the protein tyrosine kinase family. It contains N-terminal transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosporylates other proteins, and is itself also phosporylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein involves in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40723896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014916.4. 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
	LMTK2	NM_014916.4	MANE Select	c.484G>C	p.Val162Leu	missense	Exon 5 of 14	NP_055731.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMTK2	ENST00000297293.6	TSL:1 MANE Select	c.484G>C	p.Val162Leu	missense	Exon 5 of 14	ENSP00000297293.5	Q8IWU2
	LMTK2	ENST00000873831.1		c.478G>C	p.Val160Leu	missense	Exon 5 of 14	ENSP00000543890.1
	LMTK2	ENST00000930919.1		c.484G>C	p.Val162Leu	missense	Exon 5 of 13	ENSP00000600978.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	0.96	L
PhyloP100		6.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.49
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Polyphen		0.97	D
Vest4		0.42
MutPred		0.55		Loss of MoRF binding (P = 0.1669)
MVP		0.63
MPC		0.75
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.22
gMVP		0.45
Mutation Taster		=73/27	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: rs751573329; hg19: chr7-97784103;