9-117004690-C-T

Variant names:

• chr9-117004690-C-T
• rs7042036
• NM_001365068.1:c.1591+3402G>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.1591+3402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,980 control chromosomes in the GnomAD database, including 27,173 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 0.56 (27173 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1591+3402G>A		intron_variant	Intron 7 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1591+3402G>A		intron_variant	Intron 7 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1438+3402G>A		intron_variant	Intron 6 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1591+3402G>A		intron_variant	Intron 7 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1438+3402G>A		intron_variant	Intron 6 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1438+3402G>A		intron_variant	Intron 6 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.772+3402G>A		intron_variant	Intron 5 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84783 AN: 151862 Hom.: 27156 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.558 AC: 84819 AN: 151980 Hom.: 27173 Cov.: 32 AF XY: 0.561 AC XY: 41665 AN XY: 74256

African (AFR) AF: 0.212 AC: 8796 AN: 41438

American (AMR) AF: 0.711 AC: 10849 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3723 AN: 5146

South Asian (SAS) AF: 0.642 AC: 3086 AN: 4806

European-Finnish (FIN) AF: 0.620 AC: 6549 AN: 10558

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47505 AN: 67990

Other (OTH) AF: 0.596 AC: 1255 AN: 2104

Alfa AF: 0.665 Hom.: 57587

Bravo AF: 0.552

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.81
DANN	Benign	0.52
PhyloP100		-0.39
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: rs7042036; hg19: chr9-119766969;