Genetic Variant NM_014916.4:c.2433G>A (chr7-98192898-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014916.4(LMTK2):c.2433G>A(p.Pro811Pro) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

33 publications found

Variant links:

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]

LMTK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMTK2	NM_014916.4 link	c.2433G>A	p.Pro811Pro	synonymous_variant	Exon 11 of 14	ENST00000297293.6	NP_055731.2	Q8IWU2
LMTK2	XM_011515981.4 link	c.2427G>A	p.Pro809Pro	synonymous_variant	Exon 11 of 14		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6 link	c.2433G>A	p.Pro811Pro	synonymous_variant	Exon 11 of 14	1	NM_014916.4	ENSP00000297293.5		Q8IWU2

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56774

AN:

151896

Hom.:

13469

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.402

AC:

100938

AN:

251372

AF XY:

0.411

show subpopulations

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 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.:

AF XY:

0.483

AC XY:

351136

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.0972

AC:

3255

AN:

33478

American (AMR)

AF:

0.258

AC:

11543

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

15348

AN:

26130

East Asian (EAS)

AF:

0.125

AC:

4972

AN:

39700

South Asian (SAS)

AF:

0.238

AC:

20544

AN:

86250

European-Finnish (FIN)

AF:

0.479

AC:

25582

AN:

53402

Middle Eastern (MID)

AF:

0.612

AC:

3530

AN:

5768

European-Non Finnish (NFE)

AF:

0.539

AC:

599102

AN:

1111786

Other (OTH)

AF:

0.473

AC:

28572

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19844

39689

59533

79378

99222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16430

32860

49290

65720

82150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.373

AC:

56758

AN:

152014

Hom.:

13468

Cov.:

AF XY:

0.364

AC XY:

27072

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.111

AC:

4586

AN:

41488

American (AMR)

AF:

0.351

AC:

5373

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2015

AN:

3468

East Asian (EAS)

AF:

0.141

AC:

727

AN:

5160

South Asian (SAS)

AF:

0.233

AC:

1116

AN:

4800

European-Finnish (FIN)

AF:

0.463

AC:

4884

AN:

10550

Middle Eastern (MID)

AF:

0.632

AC:

182

AN:

288

European-Non Finnish (NFE)

AF:

0.538

AC:

36545

AN:

67952

Other (OTH)

AF:

0.427

AC:

900

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1513

3026

4539

6052

7565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.497

Hom.:

40965

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

(source)

DANN

Benign

0.67

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over