dbSNP rs1556943853: SLITRK2:p.Asn95Thr (chrX-145822709-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_032539.5(SLITRK2):c.284A>C(p.Asn95Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N95S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)

Failed GnomAD Quality Control

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.

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.284A>C	p.Asn95Thr	missense	Exon 5 of 5	NP_115928.1	Q9H156-1
SLITRK2	NM_001144003.3		c.284A>C	p.Asn95Thr	missense	Exon 5 of 5	NP_001137475.1	Q9H156-1
SLITRK2	NM_001144004.3		c.284A>C	p.Asn95Thr	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.284A>C	p.Asn95Thr	missense	Exon 5 of 5	ENSP00000334374.5	Q9H156-1
SLITRK2	ENST00000370490.1	TSL:6	c.284A>C	p.Asn95Thr	missense	Exon 1 of 1	ENSP00000359521.1	Q9H156-1
SLITRK2	ENST00000867861.1		c.284A>C	p.Asn95Thr	missense	Exon 5 of 5	ENSP00000537920.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111317

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33552

African (AFR)

AF:

0.00

AC:

AN:

30621

American (AMR)

AF:

0.00

AC:

AN:

10516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3503

South Asian (SAS)

AF:

0.00

AC:

AN:

2552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6037

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53104

Other (OTH)

AF:

0.00

AC:

AN:

1498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.8

PhyloP100

7.5

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.34

Sift

Uncertain

0.028

Sift4G

Benign

0.24

Polyphen

0.99

Vest4

0.84

MutPred

0.51

Gain of glycosylation at N95 (P = 0.0286)

MVP

0.81

MPC

1.5

ClinPred

0.99

GERP RS

5.1

Varity_R

0.72

gMVP

0.60

Mutation Taster

=57/43

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over