Genetic Variant SLITRK2:p.Val201Ile (chrX-145823026-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032539.5(SLITRK2):c.601G>A(p.Val201Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000778 in 1,209,541 control chromosomes in the GnomAD database, including 3 homozygotes. There are 309 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., 15 hem., cov: 22)

Exomes 𝑓: 0.00082 ( 3 hom. 294 hem. )

Consequence

SLITRK2
NM_032539.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27813387).

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5 link	c.601G>A	p.Val201Ile	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.601G>A	p.Val201Ile	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5		Q9H156-1B3KTY4
SLITRK2	ENST00000370490.1 link	c.601G>A	p.Val201Ile	missense_variant	Exon 1 of 1	6		ENSP00000359521.1		Q9H156-1

Frequencies

GnomAD3 genomes

AF:

0.000341

AC:

AN:

111352

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

AN XY:

33564

show subpopulations

Gnomad AFR

AF:

0.000196

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:

0.000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

183486

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

67916

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000822

AC:

903

AN:

1098189

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

294

AN XY:

363547

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00106

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000341

AC:

AN:

111352

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

AN XY:

33564

show subpopulations

Gnomad4 AFR

AF:

0.000196

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.V201I) alteration is located in exon 5 (coding exon 1) of the SLITRK2 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the valine (V) at amino acid position 201 to be replaced by an isoleucine (I). 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

0.085

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;T

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.070

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.15

Sift

Benign

0.10

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.98

D;D

Vest4

0.38

MVP

0.38

MPC

0.82

ClinPred

0.097

GERP RS

5.0

Varity_R

0.19

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over