chr7-98192803-T-A

Position:

• chr7-98192803-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014916.4(LMTK2):​c.2338T>A​(p.Leu780Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,613,060 control chromosomes in the GnomAD database, including 199,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (13463 hom., cov: 32)
  • Exomes 𝑓: 0.49 (185669 hom.)
• Consequence: LMTK2 NM_014916.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.071508E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMTK2	NM_014916.4	c.2338T>A	p.Leu780Met	missense_variant	11/14	ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.2332T>A	p.Leu778Met	missense_variant	11/14		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.2338T>A	p.Leu780Met	missense_variant	11/14	1	NM_014916.4	ENSP00000297293	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56768 AN: 151962 Hom.: 13464 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.402 AC: 100889 AN: 251224 Hom.: 24268 AF XY: 0.411 AC XY: 55797 AN XY: 135790

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.472

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.488 AC: 712340 AN: 1460980 Hom.: 185669 Cov.: 42 AF XY: 0.483 AC XY: 351072 AN XY: 726748

Gnomad4 AFR exome AF: 0.0973

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.373 AC: 56752 AN: 152080 Hom.: 13463 Cov.: 32 AF XY: 0.364 AC XY: 27051 AN XY: 74292

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.428

Alfa AF: 0.488 Hom.: 11296

Bravo AF: 0.361

TwinsUK AF: 0.533 AC: 1975

ALSPAC AF: 0.539 AC: 2077

ESP6500AA AF: 0.125 AC: 551

ESP6500EA AF: 0.548 AC: 4710

ExAC AF: 0.401 AC: 48697

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.94
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.000091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.17
Sift	Benign	0.073	T
Sift4G	Benign	0.23	T
Polyphen		0.76	P
Vest4		0.053
MPC		0.46
ClinPred		0.0089	T
GERP RS		-0.88
Varity_R		0.069
gMVP		0.12

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

Other links and lift over

dbSNP: rs11765552; hg19: chr7-97822115; COSMIC: COSV51997152;