9-117125435-G-T

Variant names:

• chr9-117125435-G-T
• rs1572156
• NM_001365068.1:c.1168+15891C>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.1168+15891C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,064 control chromosomes in the GnomAD database, including 4,195 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 0.23 (4195 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• 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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 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.1168+15891C>A		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.1168+15891C>A		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.1016-29284C>A		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.1168+15891C>A		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.1016-29284C>A		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000361477.8	TSL:5	c.1016-29284C>A		intron	N/A	ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35266 AN: 151946 Hom.: 4187 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.232 AC: 35286 AN: 152064 Hom.: 4195 Cov.: 33 AF XY: 0.233 AC XY: 17299 AN XY: 74336

African (AFR) AF: 0.173 AC: 7171 AN: 41470

American (AMR) AF: 0.274 AC: 4186 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5158

South Asian (SAS) AF: 0.285 AC: 1371 AN: 4812

European-Finnish (FIN) AF: 0.257 AC: 2720 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17069 AN: 67976

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.216 Hom.: 1429

Bravo AF: 0.229

Asia WGS AF: 0.278 AC: 965 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		-0.011
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: rs1572156; hg19: chr9-119887714;