NM_014916.4:c.39G>A

Variant names:

• chr7-98107216-G-A
• NM_014916.4:c.39G>A
• LMTK2 p.Leu13Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014916.4(LMTK2):​c.39G>A​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: LMTK2 NM_014916.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.964 with no splicing effect.

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.39G>A	p.Leu13Leu	synonymous	Exon 1 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.39G>A	p.Leu13Leu	synonymous	Exon 1 of 14	ENSP00000297293.5	Q8IWU2
	LMTK2	ENST00000873831.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 14	ENSP00000543890.1
	LMTK2	ENST00000930919.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 13	ENSP00000600978.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1312902 Hom.: 0 Cov.: 32 AF XY: 0.00000155 AC XY: 1 AN XY: 646314

African (AFR) AF: 0.00 AC: 0 AN: 26240

American (AMR) AF: 0.00 AC: 0 AN: 25010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22308

East Asian (EAS) AF: 0.00 AC: 0 AN: 28696

South Asian (SAS) AF: 0.00 AC: 0 AN: 71428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32534

Middle Eastern (MID) AF: 0.000252 AC: 1 AN: 3966

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048192

Other (OTH) AF: 0.00 AC: 0 AN: 54528

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.7
DANN	Benign	0.89
PhyloP100		0.96
PromoterAI		-0.0028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-97736528;