chr9-117375479-C-T

Variant names:

• chr9-117375479-C-T
• rs2226006
• NM_001365068.1:c.442+39018G>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.442+39018G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,138 control chromosomes in the GnomAD database, including 21,194 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 0.52 (21194 hom., cov: 34)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.442+39018G>A		intron_variant	Intron 1 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.442+39018G>A		intron_variant	Intron 1 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.442+39018G>A		intron_variant	Intron 1 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.442+39018G>A		intron_variant	Intron 1 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.442+39018G>A		intron_variant	Intron 1 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.442+39018G>A		intron_variant	Intron 1 of 22	5		ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79395 AN: 152020 Hom.: 21151 Cov.: 34

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.523 AC: 79495 AN: 152138 Hom.: 21194 Cov.: 34 AF XY: 0.522 AC XY: 38834 AN XY: 74346

African (AFR) AF: 0.599 AC: 24878 AN: 41510

American (AMR) AF: 0.604 AC: 9219 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2650 AN: 5172

South Asian (SAS) AF: 0.576 AC: 2780 AN: 4828

European-Finnish (FIN) AF: 0.393 AC: 4160 AN: 10574

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32687 AN: 67996

Other (OTH) AF: 0.512 AC: 1083 AN: 2114

Alfa AF: 0.494 Hom.: 78836

Bravo AF: 0.540

Asia WGS AF: 0.546 AC: 1893 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.040
DANN	Benign	0.70
PhyloP100		-2.4
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: rs2226006; hg19: chr9-120137758;