chr9-116912443-C-T

Variant names:

• chr9-116912443-C-T
• rs944323
• NM_001365068.1:c.1890-48710G>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.1890-48710G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,076 control chromosomes in the GnomAD database, including 21,785 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 0.53 (21785 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 3 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 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.1890-48710G>A		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.1878-48710G>A		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.1737-48710G>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.1890-48710G>A		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.1737-48710G>A		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.1887-48710G>A		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80088 AN: 151958 Hom.: 21765 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.527 AC: 80157 AN: 152076 Hom.: 21785 Cov.: 33 AF XY: 0.523 AC XY: 38862 AN XY: 74326

African (AFR) AF: 0.476 AC: 19726 AN: 41484

American (AMR) AF: 0.517 AC: 7909 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3466

East Asian (EAS) AF: 0.115 AC: 596 AN: 5182

South Asian (SAS) AF: 0.545 AC: 2629 AN: 4820

European-Finnish (FIN) AF: 0.550 AC: 5815 AN: 10566

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39870 AN: 67962

Other (OTH) AF: 0.524 AC: 1104 AN: 2106

Alfa AF: 0.570 Hom.: 41618

Bravo AF: 0.520

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.0
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: rs944323; hg19: chr9-119674722;