9-117164147-T-A

Variant names:

• chr9-117164147-T-A
• rs4838255
• NM_001365068.1:c.1016-22669A>T

Variant summary

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

The NM_001365068.1(ASTN2):​c.1016-22669A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,122 control chromosomes in the GnomAD database, including 56,635 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 0.86 (56635 hom., cov: 34)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.1016-22669A>T		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.1016-22669A>T		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.1015+50211A>T		intron	N/A	NP_054729.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.1016-22669A>T		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.1015+50211A>T		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.1016-22672A>T		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130967 AN: 152004 Hom.: 56584 Cov.: 34

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.862 AC: 131076 AN: 152122 Hom.: 56635 Cov.: 34 AF XY: 0.866 AC XY: 64390 AN XY: 74350

African (AFR) AF: 0.896 AC: 37202 AN: 41526

American (AMR) AF: 0.876 AC: 13379 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2865 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5130 AN: 5144

South Asian (SAS) AF: 0.904 AC: 4357 AN: 4822

European-Finnish (FIN) AF: 0.886 AC: 9403 AN: 10610

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56130 AN: 67968

Other (OTH) AF: 0.852 AC: 1800 AN: 2112

Alfa AF: 0.832 Hom.: 25677

Bravo AF: 0.863

Asia WGS AF: 0.941 AC: 3273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		1.3
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: rs4838255; hg19: chr9-119926426;