rs951987

Variant names:

• chr7-98133083-A-G
• rs951987
• NM_014916.4:c.104-4232A>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.104-4232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,236 control chromosomes in the GnomAD database, including 1,970 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 0.13 (1970 hom., cov: 32)
• Consequence: LMTK2 NM_014916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 2 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 (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMTK2	NM_014916.4	c.104-4232A>G		intron_variant	Intron 1 of 13	ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.98-4232A>G		intron_variant	Intron 1 of 13		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.104-4232A>G		intron_variant	Intron 1 of 13	1	NM_014916.4	ENSP00000297293.5
LMTK2	ENST00000493372.1	n.194-4232A>G		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19324 AN: 152118 Hom.: 1966 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.127 AC: 19356 AN: 152236 Hom.: 1970 Cov.: 32 AF XY: 0.126 AC XY: 9393 AN XY: 74456

African (AFR) AF: 0.276 AC: 11460 AN: 41484

American (AMR) AF: 0.121 AC: 1850 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.0922 AC: 478 AN: 5186

South Asian (SAS) AF: 0.170 AC: 821 AN: 4824

European-Finnish (FIN) AF: 0.0311 AC: 331 AN: 10628

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3615 AN: 68024

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.111 Hom.: 315

Bravo AF: 0.139

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.3
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: rs951987; hg19: chr7-97762395;