7-98141539-T-C

Variant names:

• chr7-98141539-T-C
• NM_014916.4:c.374T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014916.4(LMTK2):​c.374T>C​(p.Val125Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMTK2 NM_014916.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001586
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.424
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098768085).

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.374T>C	p.Val125Ala	missense splice_region	Exon 3 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.374T>C	p.Val125Ala	missense splice_region	Exon 3 of 14	ENSP00000297293.5	Q8IWU2
	LMTK2	ENST00000873831.1		c.368T>C	p.Val123Ala	missense splice_region	Exon 3 of 14	ENSP00000543890.1
	LMTK2	ENST00000930919.1		c.374T>C	p.Val125Ala	missense splice_region	Exon 3 of 13	ENSP00000600978.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.42
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.17	T
Polyphen		0.0020	B
Vest4		0.095
MutPred		0.22		Gain of ubiquitination at K129 (P = 0.0686)
MVP		0.68
MPC		0.26
ClinPred		0.16	T
GERP RS		1.5
Varity_R		0.095
gMVP		0.32
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.0020
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

hg19: chr7-97770851;