rs10491578

Variant names:

• chr9-116621609-A-G
• rs10491578
• NM_001365068.1:c.3073-1166T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):​c.3073-1166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,122 control chromosomes in the GnomAD database, including 2,489 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 0.17 (2489 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 4 publications found

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]

ASTN2 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000308541 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.3073-1166T>C		intron_variant	Intron 17 of 22	ENST00000313400.9	NP_001351997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.3073-1166T>C		intron_variant	Intron 17 of 22	5	NM_001365068.1	ENSP00000314038.4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25272 AN: 152004 Hom.: 2492 Cov.: 32

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.166 AC: 25264 AN: 152122 Hom.: 2489 Cov.: 32 AF XY: 0.163 AC XY: 12112 AN XY: 74350

African (AFR) AF: 0.0718 AC: 2982 AN: 41504

American (AMR) AF: 0.150 AC: 2290 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3468

East Asian (EAS) AF: 0.102 AC: 527 AN: 5164

South Asian (SAS) AF: 0.100 AC: 483 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15667 AN: 67988

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.216 Hom.: 7066

Bravo AF: 0.163

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.69
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs10491578; hg19: chr9-119383888;