9-116571404-C-G

Variant names:

• chr9-116571404-C-G
• rs10983238
• NM_001365068.1:c.3355+46920G>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.3355+46920G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,256 control chromosomes in the GnomAD database, including 2,520 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 0.16 (2520 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 21 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

ENSG00000230894 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 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.3355+46920G>C		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.3343+46920G>C		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.3202+46920G>C		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.3355+46920G>C		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.3202+46920G>C		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000288520.9	TSL:1	c.658+46920G>C		intron	N/A	ENSP00000288520.5	O75129-4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24675 AN: 152136 Hom.: 2520 Cov.: 33

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.162 AC: 24687 AN: 152256 Hom.: 2520 Cov.: 33 AF XY: 0.159 AC XY: 11858 AN XY: 74446

African (AFR) AF: 0.0462 AC: 1921 AN: 41558

American (AMR) AF: 0.166 AC: 2543 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 960 AN: 3472

East Asian (EAS) AF: 0.111 AC: 575 AN: 5184

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4816

European-Finnish (FIN) AF: 0.172 AC: 1825 AN: 10600

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15865 AN: 68018

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.204 Hom.: 1951

Bravo AF: 0.159

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.33
PhyloP100		-0.074
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: rs10983238; hg19: chr9-119333683;