rs10491576

Variant names:

• chr9-116778165-C-T
• rs10491576
• NM_001365068.1:c.2396+27467G>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.2396+27467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,056 control chromosomes in the GnomAD database, including 61,863 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 0.90 (61863 hom., cov: 31)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2396+27467G>A		intron_variant	Intron 13 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.2384+27467G>A		intron_variant	Intron 13 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.2243+27467G>A		intron_variant	Intron 12 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.2396+27467G>A		intron_variant	Intron 13 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.2243+27467G>A		intron_variant	Intron 12 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.2243+27467G>A		intron_variant	Intron 12 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.1565+27467G>A		intron_variant	Intron 11 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136295 AN: 151938 Hom.: 61836 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.897 AC: 136376 AN: 152056 Hom.: 61863 Cov.: 31 AF XY: 0.899 AC XY: 66824 AN XY: 74314

African (AFR) AF: 0.740 AC: 30639 AN: 41404

American (AMR) AF: 0.949 AC: 14501 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3265 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5161 AN: 5164

South Asian (SAS) AF: 0.929 AC: 4473 AN: 4814

European-Finnish (FIN) AF: 0.955 AC: 10092 AN: 10572

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65156 AN: 68026

Other (OTH) AF: 0.918 AC: 1941 AN: 2114

Alfa AF: 0.921 Hom.: 8682

Bravo AF: 0.890

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.70
PhyloP100		-1.4
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: rs10491576; hg19: chr9-119540444;