Genetic Variant SLITRK2:p.Thr296Ala (chrX-145823311-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032539.5(SLITRK2):c.886A>G(p.Thr296Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,052 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3963188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5 link	c.886A>G	p.Thr296Ala	missense_variant	Exon 5 of 5	ENST00000335565.6	NP_115928.1	Q9H156-1B3KTY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK2	ENST00000335565.6 link	c.886A>G	p.Thr296Ala	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5		Q9H156-1B3KTY4
SLITRK2	ENST00000370490.1 link	c.886A>G	p.Thr296Ala	missense_variant	Exon 1 of 1	6		ENSP00000359521.1		Q9H156-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098052

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.886A>G (p.T296A) alteration is located in exon 5 (coding exon 1) of the SLITRK2 gene. This alteration results from a A to G substitution at nucleotide position 886, causing the threonine (T) at amino acid position 296 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Jul 09, 2024

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

.;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.12

Sift

Benign

0.071

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.78

P;P

Vest4

0.36

MutPred

0.26

Loss of glycosylation at T296 (P = 0.0059);Loss of glycosylation at T296 (P = 0.0059);

MVP

0.85

MPC

0.60

ClinPred

0.83

GERP RS

5.7

Varity_R

0.41

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over