9-116728293-A-G

Variant names:

• chr9-116728293-A-G
• rs7028544
• NM_001365068.1:c.2626+699T>C

Variant summary

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

The NM_001365068.1(ASTN2):​c.2626+699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,030 control chromosomes in the GnomAD database, including 9,244 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 0.33 (9244 hom., cov: 31)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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 = 0.485 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.2626+699T>C		intron	N/A	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.2614+699T>C		intron	N/A	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.2473+699T>C		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.2626+699T>C		intron	N/A	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.2473+699T>C		intron	N/A	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.2623+699T>C		intron	N/A	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50204 AN: 151912 Hom.: 9244 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.330 AC: 50212 AN: 152030 Hom.: 9244 Cov.: 31 AF XY: 0.333 AC XY: 24741 AN XY: 74280

African (AFR) AF: 0.179 AC: 7410 AN: 41488

American (AMR) AF: 0.267 AC: 4076 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2577 AN: 5144

South Asian (SAS) AF: 0.422 AC: 2020 AN: 4784

European-Finnish (FIN) AF: 0.466 AC: 4923 AN: 10562

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26713 AN: 67986

Other (OTH) AF: 0.340 AC: 718 AN: 2112

Alfa AF: 0.368 Hom.: 21050

Bravo AF: 0.306

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.51
PhyloP100		-0.25
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: rs7028544; hg19: chr9-119490572;