X-145822674-C-G

Variant names:

• chrX-145822674-C-G
• rs376893929
• NM_032539.5:c.249C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_032539.5(SLITRK2):​c.249C>G​(p.Val83Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,209,832 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 148 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 5 hem., cov: 21)
  • Exomes 𝑓: 0.00039 (0 hom. 143 hem.)
• Consequence: SLITRK2 NM_032539.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked 111

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant X-145822674-C-G is Benign according to our data. Variant chrX-145822674-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2661583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK2	NM_032539.5	MANE Select	c.249C>G	p.Val83Val	synonymous	Exon 5 of 5	NP_115928.1	Q9H156-1
	SLITRK2	NM_001144003.3		c.249C>G	p.Val83Val	synonymous	Exon 5 of 5	NP_001137475.1	Q9H156-1
	SLITRK2	NM_001144004.3		c.249C>G	p.Val83Val	synonymous	Exon 5 of 5	NP_001137476.1	Q9H156-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK2	ENST00000335565.6	TSL:2 MANE Select	c.249C>G	p.Val83Val	synonymous	Exon 5 of 5	ENSP00000334374.5	Q9H156-1
	SLITRK2	ENST00000370490.1	TSL:6	c.249C>G	p.Val83Val	synonymous	Exon 1 of 1	ENSP00000359521.1	Q9H156-1
	SLITRK2	ENST00000867861.1		c.249C>G	p.Val83Val	synonymous	Exon 5 of 5	ENSP00000537920.1

Frequencies

GnomAD3 genomes AF: 0.000260 AC: 29 AN: 111587 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00795

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000767

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00134

GnomAD2 exomes AF: 0.000458 AC: 84 AN: 183490 AF XY: 0.000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000386 AC: 424 AN: 1098193 Hom.: 0 Cov.: 30 AF XY: 0.000393 AC XY: 143 AN XY: 363547

African (AFR) AF: 0.0000379 AC: 1 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00815 AC: 158 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000923 AC: 5 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000273 AC: 230 AN: 842088

Other (OTH) AF: 0.000651 AC: 30 AN: 46095

GnomAD4 genome AF: 0.000260 AC: 29 AN: 111639 Hom.: 0 Cov.: 21 AF XY: 0.000148 AC XY: 5 AN XY: 33815

African (AFR) AF: 0.0000326 AC: 1 AN: 30693

American (AMR) AF: 0.00 AC: 0 AN: 10567

Ashkenazi Jewish (ASJ) AF: 0.00795 AC: 21 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.000769 AC: 2 AN: 2600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53151

Other (OTH) AF: 0.00133 AC: 2 AN: 1509

Alfa AF: 0.00126 Hom.: 8

Bravo AF: 0.000249

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs376893929; hg19: chrX-144904192; COSMIC: COSV59424864; COSMIC: COSV59424864;