rs10491574

Positions:

• chr9-116860159-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):​c.2040+3424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,068 control chromosomes in the GnomAD database, including 2,297 homozygotes. 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: 𝑓 0.16 (2297 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

Genes affected

ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

ENSG00000285820 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2040+3424G>A		intron_variant		ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.2028+3424G>A		intron_variant			NP_001351998.1
ASTN2	NM_014010.5	c.1887+3424G>A		intron_variant			NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.2040+3424G>A		intron_variant		5	NM_001365068.1	ENSP00000314038.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23999 AN: 151950 Hom.: 2303 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 23992 AN: 152068 Hom.: 2297 Cov.: 33 AF XY: 0.160 AC XY: 11927 AN XY: 74346

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.159

Alfa AF: 0.129 Hom.: 2149

Bravo AF: 0.175

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.51

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: rs10491574; hg19: chr9-119622438;