rs11765552

Variant names:

• chr7-98192803-T-A
• rs11765552
• NM_014916.4:c.2338T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-98192803-T-A
• chr7-98192803-T-C
• chr7-98192803-T-G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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: 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
• Publications: 45 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: Benign. The variant received -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.

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.2338T>A	p.Leu780Met	missense	Exon 11 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.2338T>A	p.Leu780Met	missense	Exon 11 of 14	ENSP00000297293.5	Q8IWU2
	LMTK2	ENST00000873831.1		c.2332T>A	p.Leu778Met	missense	Exon 11 of 14	ENSP00000543890.1
	LMTK2	ENST00000930919.1		c.2338T>A	p.Leu780Met	missense	Exon 11 of 13	ENSP00000600978.1

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

GnomAD2 exomes AF: 0.402 AC: 100889 AN: 251224 AF XY: 0.411

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 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

African (AFR) AF: 0.0973 AC: 3256 AN: 33462

American (AMR) AF: 0.258 AC: 11530 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15345 AN: 26126

East Asian (EAS) AF: 0.125 AC: 4972 AN: 39680

South Asian (SAS) AF: 0.238 AC: 20544 AN: 86200

European-Finnish (FIN) AF: 0.479 AC: 25580 AN: 53394

Middle Eastern (MID) AF: 0.612 AC: 3529 AN: 5766

European-Non Finnish (NFE) AF: 0.539 AC: 599013 AN: 1111306

Other (OTH) AF: 0.473 AC: 28571 AN: 60354

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

African (AFR) AF: 0.110 AC: 4576 AN: 41526

American (AMR) AF: 0.351 AC: 5374 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2017 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1107 AN: 4802

European-Finnish (FIN) AF: 0.464 AC: 4882 AN: 10528

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36557 AN: 67976

Other (OTH) AF: 0.428 AC: 899 AN: 2102

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 v4.9

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
PhyloP100		0.63
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
Mutation Taster		=100/0	polymorphism (auto)

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