Genetic Variant NM_032539.5:c.181C>A (chrX-145822606-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032539.5(SLITRK2):c.181C>A(p.Gln61Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18481854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5 link	c.181C>A	p.Gln61Lys	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.181C>A	p.Gln61Lys	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5		Q9H156-1B3KTY4
SLITRK2	ENST00000370490.1 link	c.181C>A	p.Gln61Lys	missense_variant	Exon 1 of 1	6		ENSP00000359521.1		Q9H156-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000182

AC:

AN:

1097697

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363053

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:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.181C>A (p.Q61K) alteration is located in exon 5 (coding exon 1) of the SLITRK2 gene. This alteration results from a C to A substitution at nucleotide position 181, causing the glutamine (Q) at amino acid position 61 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.011

T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.089

Sift

Benign

1.0

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0020

B;B

Vest4

0.23

MutPred

0.50

Gain of methylation at Q61 (P = 0.0173);Gain of methylation at Q61 (P = 0.0173);

MVP

0.61

MPC

0.69

ClinPred

0.73

GERP RS

5.0

Varity_R

0.36

gMVP

0.44

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

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