7-98178570-C-A

Variant names:

• chr7-98178570-C-A
• rs6965016
• NM_014916.4:c.792-6481C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMTK2	NM_014916.4	MANE Select	c.792-6481C>A		intron	N/A	NP_055731.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMTK2	ENST00000297293.6	TSL:1 MANE Select	c.792-6481C>A		intron	N/A	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

African (AFR) AF: 0.112 AC: 4631 AN: 41530

American (AMR) AF: 0.351 AC: 5363 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2011 AN: 3466

East Asian (EAS) AF: 0.141 AC: 727 AN: 5168

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4878 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36409 AN: 67970

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.476 Hom.: 7963

Bravo AF: 0.360

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.80
PhyloP100		2.8
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: rs6965016; hg19: chr7-97807882;