X-145822480-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_032539.5(SLITRK2):c.55A>G(p.Thr19Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,209,133 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Publications

0 publications found

Variant links:

Genes affected

SLITRK2 (HGNC:13449): (SLIT and NTRK like family member 2) This gene encodes an integral membrane protein that contains two N-terminal leucine-rich repeats domains and contains C-terminal regions similar to neurotrophin receptors. The encoded protein may play a role in modulating neurite activity. Alternatively spliced transcript variants encoding the same protein have been described.[provided by RefSeq, Feb 2010]

SLITRK2 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked 111
Inheritance: XL Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

SLITRK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.1956 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder, X-linked 111.

BP4

Computational evidence support a benign effect (MetaRNN=0.09854415).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK2	NM_032539.5	MANE Select	c.55A>G	p.Thr19Ala	missense	Exon 5 of 5	NP_115928.1	Q9H156-1
SLITRK2	NM_001144003.3		c.55A>G	p.Thr19Ala	missense	Exon 5 of 5	NP_001137475.1	Q9H156-1
SLITRK2	NM_001144004.3		c.55A>G	p.Thr19Ala	missense	Exon 5 of 5	NP_001137476.1	Q9H156-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLITRK2	ENST00000335565.6	TSL:2 MANE Select	c.55A>G	p.Thr19Ala	missense	Exon 5 of 5	ENSP00000334374.5	Q9H156-1
SLITRK2	ENST00000370490.1	TSL:6	c.55A>G	p.Thr19Ala	missense	Exon 1 of 1	ENSP00000359521.1	Q9H156-1
SLITRK2	ENST00000867861.1		c.55A>G	p.Thr19Ala	missense	Exon 5 of 5	ENSP00000537920.1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000547

AC:

AN:

182962

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1097759

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363117

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.000284

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

54100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841772

Other (OTH)

AF:

0.00

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000180

AC:

AN:

111374

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30536

American (AMR)

AF:

0.000190

AC:

AN:

10529

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3533

South Asian (SAS)

AF:

0.00

AC:

AN:

2631

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53084

Other (OTH)

AF:

0.00

AC:

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.012

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

M_CAP

Benign

0.012

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

4.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.38

REVEL

Benign

0.21

Sift

Benign

0.49

Sift4G

Benign

0.93

Polyphen

0.0010

Vest4

0.20

MutPred

0.29

Gain of ubiquitination at K23 (P = 0.1103)

MVP

0.83

MPC

0.53

ClinPred

0.086

GERP RS

4.6

Varity_R

0.095

gMVP

0.53

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over