rs1888286

Variant names:

• chr9-116963772-T-C
• rs1888286
• NM_001365068.1:c.1889+11436A>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.1889+11436A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,932 control chromosomes in the GnomAD database, including 11,224 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 0.37 (11224 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 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.1889+11436A>G		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.1877+11436A>G		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.1736+11436A>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.1889+11436A>G		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.1736+11436A>G		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000361477.8	TSL:5	c.1736+11436A>G		intron	N/A	ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55664 AN: 151814 Hom.: 11193 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.367 AC: 55749 AN: 151932 Hom.: 11224 Cov.: 32 AF XY: 0.364 AC XY: 27043 AN XY: 74244

African (AFR) AF: 0.534 AC: 22107 AN: 41406

American (AMR) AF: 0.403 AC: 6150 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3464

East Asian (EAS) AF: 0.297 AC: 1534 AN: 5162

South Asian (SAS) AF: 0.190 AC: 917 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3213 AN: 10558

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.288 AC: 19587 AN: 67948

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.335 Hom.: 1284

Bravo AF: 0.387

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		-0.46
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: rs1888286; hg19: chr9-119726051;