chr9-117291742-C-T

Variant names:

• chr9-117291742-C-T
• rs7862566
• NM_001365068.1:c.443-229G>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.443-229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,112 control chromosomes in the GnomAD database, including 2,664 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 0.18 (2664 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.443-229G>A		intron_variant	Intron 1 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.443-229G>A		intron_variant	Intron 1 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.443-229G>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.443-229G>A		intron_variant	Intron 1 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.443-229G>A		intron_variant	Intron 1 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.443-229G>A		intron_variant	Intron 1 of 22	5		ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27186 AN: 151994 Hom.: 2670 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.179 AC: 27189 AN: 152112 Hom.: 2664 Cov.: 33 AF XY: 0.189 AC XY: 14033 AN XY: 74342

African (AFR) AF: 0.178 AC: 7379 AN: 41488

American (AMR) AF: 0.242 AC: 3699 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1616 AN: 5168

South Asian (SAS) AF: 0.316 AC: 1525 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2455 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9353 AN: 67990

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.157 Hom.: 3397

Bravo AF: 0.177

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7862566; hg19: chr9-120054021;