chrX-145822769-T-C

Variant names:

• chrX-145822769-T-C
• NM_032539.5:c.344T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032539.5(SLITRK2):​c.344T>C​(p.Leu115Pro) 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. 12/20 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLITRK2 NM_032539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5	c.344T>C	p.Leu115Pro	missense_variant	Exon 5 of 5	ENST00000335565.6	NP_115928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK2	ENST00000335565.6	c.344T>C	p.Leu115Pro	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5
SLITRK2	ENST00000370490.1	c.344T>C	p.Leu115Pro	missense_variant	Exon 1 of 1	6		ENSP00000359521.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.344T>C (p.L115P) alteration is located in exon 5 (coding exon 1) of the SLITRK2 gene. This alteration results from a T to C substitution at nucleotide position 344, causing the leucine (L) at amino acid position 115 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	4.2	H;H
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.97
MutPred		0.80		Loss of stability (P = 0.002);Loss of stability (P = 0.002);
MVP		0.82
MPC		1.9
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.98
gMVP		0.98

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-144904287;