rs1372328

Variant names:

• chr9-116722249-C-T
• rs1372328
• NM_001365068.1:c.2806+3522G>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.2806+3522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,268 control chromosomes in the GnomAD database, including 14,236 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 0.42 (14236 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.544 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.2806+3522G>A		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.2794+3522G>A		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.2653+3522G>A		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.2806+3522G>A		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.2653+3522G>A		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.2803+3522G>A		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64149 AN: 151154 Hom.: 14232 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.424 AC: 64187 AN: 151268 Hom.: 14236 Cov.: 33 AF XY: 0.426 AC XY: 31489 AN XY: 73928

African (AFR) AF: 0.293 AC: 11946 AN: 40754

American (AMR) AF: 0.554 AC: 8475 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1653 AN: 5168

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4810

European-Finnish (FIN) AF: 0.506 AC: 5326 AN: 10530

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31856 AN: 67934

Other (OTH) AF: 0.454 AC: 958 AN: 2108

Alfa AF: 0.457 Hom.: 27166

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.25
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: rs1372328; hg19: chr9-119484528;