9-116500349-G-A

Variant names:

• chr9-116500349-G-A
• rs11788366
• NM_001365068.1:c.3356-12849C>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.3356-12849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 152,258 control chromosomes in the GnomAD database, including 221 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 0.043 (221 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0651 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.3356-12849C>T		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.3344-12849C>T		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.3203-12849C>T		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.3356-12849C>T		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.3203-12849C>T		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000288520.9	TSL:1	c.659-12849C>T		intron	N/A	ENSP00000288520.5

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6478 AN: 152140 Hom.: 220 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0425 AC: 6478 AN: 152258 Hom.: 221 Cov.: 33 AF XY: 0.0406 AC XY: 3021 AN XY: 74446

African (AFR) AF: 0.0113 AC: 468 AN: 41562

American (AMR) AF: 0.0328 AC: 502 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 115 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4828

European-Finnish (FIN) AF: 0.0526 AC: 557 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0667 AC: 4538 AN: 68010

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0620 Hom.: 179

Bravo AF: 0.0395

Asia WGS AF: 0.0170 AC: 60 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	7.6
DANN	Benign	0.58
PhyloP100		0.77
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: rs11788366; hg19: chr9-119262628;