rs951988

Positions:

• chr7-98133162-C-G
• chr7-98133162-C-T

Variant summary

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

The NM_014916.4(LMTK2):​c.104-4153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,020 control chromosomes in the GnomAD database, including 13,367 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 0.41 (13367 hom., cov: 32)
• Consequence: LMTK2 NM_014916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMTK2	NM_014916.4	c.104-4153C>G		intron_variant		ENST00000297293.6
LMTK2	XM_011515981.4	c.98-4153C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMTK2	ENST00000297293.6	c.104-4153C>G		intron_variant		1	NM_014916.4	P1
LMTK2	ENST00000493372.1	n.194-4153C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62529 AN: 151902 Hom.: 13329 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.412 AC: 62624 AN: 152020 Hom.: 13367 Cov.: 32 AF XY: 0.416 AC XY: 30897 AN XY: 74302

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.345

Alfa AF: 0.245 Hom.: 554

Bravo AF: 0.403

Asia WGS AF: 0.464 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs951988; hg19: chr7-97762474;