rs10817974

Variant names:

• chr9-117013327-C-A
• rs10817974
• NM_001365068.1:c.1424-5068G>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.1424-5068G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,564 control chromosomes in the GnomAD database, including 22,209 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 (22209 hom., cov: 30)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 1 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 = 0.701 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.1424-5068G>T		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.1424-5068G>T		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.1271-5068G>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.1424-5068G>T		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.1271-5068G>T		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.1421-5068G>T		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80660 AN: 151448 Hom.: 22193 Cov.: 30

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.533 AC: 80722 AN: 151564 Hom.: 22209 Cov.: 30 AF XY: 0.536 AC XY: 39698 AN XY: 74070

African (AFR) AF: 0.406 AC: 16776 AN: 41284

American (AMR) AF: 0.625 AC: 9517 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3470

East Asian (EAS) AF: 0.720 AC: 3710 AN: 5154

South Asian (SAS) AF: 0.500 AC: 2396 AN: 4794

European-Finnish (FIN) AF: 0.562 AC: 5873 AN: 10458

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.572 AC: 38783 AN: 67860

Other (OTH) AF: 0.547 AC: 1153 AN: 2106

Alfa AF: 0.552 Hom.: 19038

Bravo AF: 0.535

Asia WGS AF: 0.569 AC: 1976 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.56
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: rs10817974; hg19: chr9-119775606;