rs3801294

Positions:

• chr7-98192898-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014916.4(LMTK2):​c.2433G>A​(p.Pro811=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,613,644 control chromosomes in the GnomAD database, including 199,093 homozygotes. In-silico tool predicts 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 (13468 hom., cov: 32)
  • Exomes 𝑓: 0.49 (185625 hom.)
• Consequence: LMTK2 NM_014916.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• 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.2433G>A	p.Pro811=	synonymous_variant	11/14	ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.2427G>A	p.Pro809=	synonymous_variant	11/14		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.2433G>A	p.Pro811=	synonymous_variant	11/14	1	NM_014916.4	ENSP00000297293	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56774 AN: 151896 Hom.: 13469 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.430

GnomAD3 exomes AF: 0.402 AC: 100938 AN: 251372 Hom.: 24275 AF XY: 0.411 AC XY: 55821 AN XY: 135878

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: 0.479

GnomAD4 exome AF: 0.487 AC: 712448 AN: 1461630 Hom.: 185625 Cov.: 44 AF XY: 0.483 AC XY: 351136 AN XY: 727120

Gnomad4 AFR exome AF: 0.0972

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: 56758 AN: 152014 Hom.: 13468 Cov.: 32 AF XY: 0.364 AC XY: 27072 AN XY: 74288

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.427

Alfa AF: 0.511 Hom.: 29049

Bravo AF: 0.361

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.44
DANN	Benign	0.67

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: rs3801294; hg19: chr7-97822210; COSMIC: COSV52000922;