9-116445327-T-C

Variant names:

• chr9-116445327-T-C
• rs888401
• NM_001365068.1:c.3498-2774A>G

Variant summary

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

The NM_001365068.1(ASTN2):​c.3498-2774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,042 control chromosomes in the GnomAD database, including 11,882 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 0.38 (11882 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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.3498-2774A>G		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.3486-2774A>G		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.3345-2774A>G		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.3498-2774A>G		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.3345-2774A>G		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000288520.9	TSL:1	c.801-2774A>G		intron	N/A	ENSP00000288520.5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58428 AN: 151924 Hom.: 11869 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.385 AC: 58491 AN: 152042 Hom.: 11882 Cov.: 32 AF XY: 0.392 AC XY: 29158 AN XY: 74306

African (AFR) AF: 0.394 AC: 16350 AN: 41482

American (AMR) AF: 0.472 AC: 7199 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.662 AC: 3428 AN: 5176

South Asian (SAS) AF: 0.613 AC: 2952 AN: 4812

European-Finnish (FIN) AF: 0.350 AC: 3692 AN: 10548

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.330 AC: 22425 AN: 67976

Other (OTH) AF: 0.370 AC: 781 AN: 2112

Alfa AF: 0.341 Hom.: 5008

Bravo AF: 0.395

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs888401; hg19: chr9-119207606;