X-145822646-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_032539.5(SLITRK2):​c.221T>C​(p.Leu74Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

SLITRK2
NM_032539.5 missense

Scores

10
5
2

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.02
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.942
PP5
Variant X-145822646-T-C is Pathogenic according to our data. Variant chrX-145822646-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1334906.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLITRK2NM_032539.5 linkc.221T>C p.Leu74Ser 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
SLITRK2ENST00000335565.6 linkc.221T>C p.Leu74Ser missense_variant Exon 5 of 5 2 NM_032539.5 ENSP00000334374.5 Q9H156-1B3KTY4
SLITRK2ENST00000370490.1 linkc.221T>C p.Leu74Ser missense_variant Exon 1 of 1 6 ENSP00000359521.1 Q9H156-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Intellectual disability Pathogenic:1
Jan 24, 2022
Diagnostic Laboratory, Strasbourg University Hospital
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing;in vitro

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
.;D
M_CAP
Uncertain
0.28
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Pathogenic
4.0
H;H
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.89
MutPred
0.78
Loss of stability (P = 0.0791);Loss of stability (P = 0.0791);
MVP
0.76
MPC
1.7
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.88
gMVP
0.92

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.

Other links and lift over

hg19: chrX-144904164; API