chr7-98141521-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014916.4(LMTK2):​c.356C>T​(p.Ser119Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,613,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

LMTK2
NM_014916.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.37
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11069623).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LMTK2NM_014916.4 linkuse as main transcriptc.356C>T p.Ser119Leu missense_variant 3/14 ENST00000297293.6
LMTK2XM_011515981.4 linkuse as main transcriptc.350C>T p.Ser117Leu missense_variant 3/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LMTK2ENST00000297293.6 linkuse as main transcriptc.356C>T p.Ser119Leu missense_variant 3/141 NM_014916.4 P1
LMTK2ENST00000493372.1 linkuse as main transcriptn.446C>T non_coding_transcript_exon_variant 3/44

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251268
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135792
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:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000479
AC:
70
AN:
1461776
Hom.:
1
Cov.:
31
AF XY:
0.0000578
AC XY:
42
AN XY:
727194
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:
0.000441
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.20
Sift
Uncertain
0.018
D
Sift4G
Benign
0.25
T
Polyphen
0.27
B
Vest4
0.39
MVP
0.61
MPC
0.27
ClinPred
0.19
T
GERP RS
4.3
Varity_R
0.17
gMVP
0.24

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs749372914; hg19: chr7-97770833; COSMIC: COSV99807513; API