rs6965016

Positions:

• chr7-98178570-C-A
• chr7-98178570-C-G
• chr7-98178570-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014916.4(LMTK2):​c.792-6481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,106 control chromosomes in the GnomAD database, including 13,387 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 (13387 hom., cov: 32)
• Consequence: LMTK2 NM_014916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMTK2	NM_014916.4	c.792-6481C>A		intron_variant		ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.786-6481C>A		intron_variant			XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.792-6481C>A		intron_variant		1	NM_014916.4	ENSP00000297293.5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56657 AN: 151986 Hom.: 13388 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.429

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.372 AC: 56647 AN: 152106 Hom.: 13387 Cov.: 32 AF XY: 0.364 AC XY: 27026 AN XY: 74342

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.426

Alfa AF: 0.441 Hom.: 3743

Bravo AF: 0.360

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.80

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: rs6965016; hg19: chr7-97807882;