chr7-98190764-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014916.4(LMTK2):​c.1035T>A​(p.Asn345Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 6.8e-7 ( 0 hom. )

Consequence

LMTK2
NM_014916.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.349
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4177123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMTK2NM_014916.4 linkc.1035T>A p.Asn345Lys missense_variant Exon 10 of 14 ENST00000297293.6 NP_055731.2 Q8IWU2
LMTK2XM_011515981.4 linkc.1029T>A p.Asn343Lys missense_variant Exon 10 of 14 XP_011514283.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMTK2ENST00000297293.6 linkc.1035T>A p.Asn345Lys missense_variant Exon 10 of 14 1 NM_014916.4 ENSP00000297293.5 Q8IWU2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251446
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135898
show subpopulations
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 SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.090
Eigen_PC
Benign
-0.027
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.14
Sift
Benign
0.29
T
Sift4G
Benign
0.36
T
Polyphen
0.74
P
Vest4
0.54
MutPred
0.60
Gain of methylation at N345 (P = 0.0121);
MVP
0.59
MPC
0.79
ClinPred
0.71
D
GERP RS
3.0
Varity_R
0.098
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755345580; hg19: chr7-97820076; API