7-98107199-C-T

Variant names:

• chr7-98107199-C-T
• rs529811468
• NM_014916.4:c.22C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014916.4(LMTK2):​c.22C>T​(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,453,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: LMTK2 NM_014916.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.824
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008303553).

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.22C>T	p.Arg8Trp	missense	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.22C>T	p.Arg8Trp	missense	Exon 1 of 14	ENSP00000297293.5	Q8IWU2
	LMTK2	ENST00000873831.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 14	ENSP00000543890.1
	LMTK2	ENST00000930919.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 13	ENSP00000600978.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000450 AC: 27 AN: 59956 AF XY: 0.000457

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000588

GnomAD4 exome AF: 0.000111 AC: 145 AN: 1301714 Hom.: 1 Cov.: 31 AF XY: 0.000137 AC XY: 88 AN XY: 640082

African (AFR) AF: 0.00 AC: 0 AN: 25796

American (AMR) AF: 0.00 AC: 0 AN: 22566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21626

East Asian (EAS) AF: 0.00 AC: 0 AN: 28530

South Asian (SAS) AF: 0.00169 AC: 118 AN: 69984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3860

European-Non Finnish (NFE) AF: 0.0000115 AC: 12 AN: 1043246

Other (OTH) AF: 0.000278 AC: 15 AN: 54016

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.000166 AC: 13

Asia WGS AF: 0.000579 AC: 2 AN: 3470

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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.82
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.27
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.042	D
Polyphen		0.98	D
Vest4		0.24
MVP		0.45
MPC		0.37
ClinPred		0.11	T
GERP RS		1.8
PromoterAI		0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.11
gMVP		0.48
Mutation Taster		=99/1	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: rs529811468; hg19: chr7-97736511; COSMIC: COSV51989730;