chr9-117053700-G-A

Variant names:

• chr9-117053700-G-A
• rs1334071
• NM_001365068.1:c.1277-13735C>T

Variant summary

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

The NM_001365068.1(ASTN2):​c.1277-13735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,830 control chromosomes in the GnomAD database, including 16,891 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 0.47 (16891 hom., cov: 31)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.1277-13735C>T		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.1277-13735C>T		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.1124-13735C>T		intron	N/A	NP_054729.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.1277-13735C>T		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.1124-13735C>T		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.1274-13735C>T		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70677 AN: 151710 Hom.: 16890 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.466 AC: 70696 AN: 151830 Hom.: 16891 Cov.: 31 AF XY: 0.467 AC XY: 34667 AN XY: 74172

African (AFR) AF: 0.382 AC: 15805 AN: 41390

American (AMR) AF: 0.366 AC: 5593 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1554 AN: 3462

East Asian (EAS) AF: 0.681 AC: 3469 AN: 5096

South Asian (SAS) AF: 0.598 AC: 2878 AN: 4814

European-Finnish (FIN) AF: 0.487 AC: 5121 AN: 10524

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34626 AN: 67954

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.473 Hom.: 2558

Bravo AF: 0.450

Asia WGS AF: 0.601 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.019
DANN	Benign	0.39
PhyloP100		-1.8
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: rs1334071; hg19: chr9-119815979;