rs1016730

Variant names:

• chr9-117225050-A-T
• rs1016730
• NM_001365068.1:c.631-10308T>A

Variant summary

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

The NM_001365068.1(ASTN2):​c.631-10308T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,026 control chromosomes in the GnomAD database, including 23,283 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 0.54 (23283 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 5 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

LOC105376237 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.631-10308T>A		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.631-10308T>A		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.631-10308T>A		intron	N/A	NP_054729.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.631-10308T>A		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.631-10308T>A		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000882685.1		c.631-10308T>A		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82491 AN: 151908 Hom.: 23270 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.543 AC: 82524 AN: 152026 Hom.: 23283 Cov.: 32 AF XY: 0.544 AC XY: 40445 AN XY: 74294

African (AFR) AF: 0.404 AC: 16768 AN: 41460

American (AMR) AF: 0.667 AC: 10194 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1702 AN: 3468

East Asian (EAS) AF: 0.859 AC: 4422 AN: 5150

South Asian (SAS) AF: 0.625 AC: 3013 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5466 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39019 AN: 67978

Other (OTH) AF: 0.566 AC: 1195 AN: 2112

Alfa AF: 0.555 Hom.: 2951

Bravo AF: 0.549

Asia WGS AF: 0.720 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.81
PhyloP100		-0.0080
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: rs1016730; hg19: chr9-119987329;