9-116490350-A-G

Variant names:

• chr9-116490350-A-G
• rs6478241
• NM_001365068.1:c.3356-2850T>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.3356-2850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 143,168 control chromosomes in the GnomAD database, including 22,872 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 0.55 (22872 hom., cov: 21)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 41 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.667 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.3356-2850T>C		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.3344-2850T>C		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.3203-2850T>C		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.3356-2850T>C		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.3203-2850T>C		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000288520.9	TSL:1	c.659-2850T>C		intron	N/A	ENSP00000288520.5

Frequencies

GnomAD3 genomes AF: 0.547 AC: 78323 AN: 143092 Hom.: 22856 Cov.: 21

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.616

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.547 AC: 78357 AN: 143168 Hom.: 22872 Cov.: 21 AF XY: 0.549 AC XY: 37837 AN XY: 68936

African (AFR) AF: 0.325 AC: 12556 AN: 38686

American (AMR) AF: 0.629 AC: 8666 AN: 13772

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2165 AN: 3426

East Asian (EAS) AF: 0.641 AC: 2980 AN: 4652

South Asian (SAS) AF: 0.687 AC: 3045 AN: 4432

European-Finnish (FIN) AF: 0.605 AC: 5214 AN: 8618

Middle Eastern (MID) AF: 0.621 AC: 174 AN: 280

European-Non Finnish (NFE) AF: 0.632 AC: 41970 AN: 66442

Other (OTH) AF: 0.557 AC: 1096 AN: 1966

Alfa AF: 0.610 Hom.: 128870

Bravo AF: 0.539

Asia WGS AF: 0.625 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.74
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: rs6478241; hg19: chr9-119252629;