rs1334098

Variant names:

• chr9-117105487-T-C
• rs1334098
• NM_001365068.1:c.1169-9336A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):​c.1169-9336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,124 control chromosomes in the GnomAD database, including 552 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 0.058 (552 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1169-9336A>G		intron_variant	Intron 4 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1169-9336A>G		intron_variant	Intron 4 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1016-9336A>G		intron_variant	Intron 3 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1169-9336A>G		intron_variant	Intron 4 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1016-9336A>G		intron_variant	Intron 3 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1016-9336A>G		intron_variant	Intron 3 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.350-9336A>G		intron_variant	Intron 2 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8825 AN: 152006 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0581 AC: 8843 AN: 152124 Hom.: 552 Cov.: 32 AF XY: 0.0596 AC XY: 4433 AN XY: 74374

African (AFR) AF: 0.128 AC: 5302 AN: 41506

American (AMR) AF: 0.101 AC: 1548 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3466

East Asian (EAS) AF: 0.186 AC: 956 AN: 5148

South Asian (SAS) AF: 0.0943 AC: 453 AN: 4804

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.00474 AC: 322 AN: 68000

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0429 Hom.: 41

Bravo AF: 0.0685

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.12
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: rs1334098; hg19: chr9-119867766;