chr9-116782154-T-C

Variant names:

• chr9-116782154-T-C
• rs4837864
• NM_001365068.1:c.2396+23478A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):​c.2396+23478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,100 control chromosomes in the GnomAD database, including 53,982 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 0.84 (53982 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 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.2396+23478A>G		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.2384+23478A>G		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.2243+23478A>G		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.2396+23478A>G		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.2243+23478A>G		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000882685.1		c.2393+23478A>G		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127883 AN: 151982 Hom.: 53955 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.841 AC: 127959 AN: 152100 Hom.: 53982 Cov.: 32 AF XY: 0.836 AC XY: 62177 AN XY: 74352

African (AFR) AF: 0.775 AC: 32124 AN: 41470

American (AMR) AF: 0.866 AC: 13239 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2927 AN: 3468

East Asian (EAS) AF: 0.802 AC: 4142 AN: 5166

South Asian (SAS) AF: 0.763 AC: 3666 AN: 4806

European-Finnish (FIN) AF: 0.807 AC: 8553 AN: 10600

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60414 AN: 67988

Other (OTH) AF: 0.849 AC: 1795 AN: 2114

Alfa AF: 0.876 Hom.: 98215

Bravo AF: 0.846

Asia WGS AF: 0.765 AC: 2662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		0.99
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: rs4837864; hg19: chr9-119544433;