NM_032539.5:c.793A>G

Variant names:

• chrX-145823218-A-G
• rs2073056207
• NM_032539.5:c.793A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032539.5(SLITRK2):​c.793A>G​(p.Arg265Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: SLITRK2 NM_032539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718

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 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=0.40620875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK2	NM_032539.5	c.793A>G	p.Arg265Gly	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.793A>G	p.Arg265Gly	missense_variant	Exon 5 of 5	2	NM_032539.5	ENSP00000334374.5
SLITRK2	ENST00000370490.1	c.793A>G	p.Arg265Gly	missense_variant	Exon 1 of 1	6		ENSP00000359521.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.793A>G (p.R265G) 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 793, causing the arginine (R) at amino acid position 265 to be replaced by a glycine (G). 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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.22	T;D
Sift4G	Benign	0.40	T;T
Polyphen		1.0	D;D
Vest4		0.78
MutPred		0.38		Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);
MVP		0.83
MPC		1.7
ClinPred		0.89	D
GERP RS		3.3
Varity_R		0.51
gMVP		0.76

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

Other links and lift over

dbSNP: rs2073056207; hg19: chrX-144904736;