rs1928984

Variant names:

• chr9-116971678-C-G
• rs1928984
• NM_001365068.1:c.1889+3530G>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.1889+3530G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,114 control chromosomes in the GnomAD database, including 6,264 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 0.28 (6264 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.1889+3530G>C		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.1877+3530G>C		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.1736+3530G>C		intron	N/A	NP_054729.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.1889+3530G>C		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.1736+3530G>C		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000361477.8	TSL:5	c.1736+3530G>C		intron	N/A	ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42603 AN: 151998 Hom.: 6250 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.280 AC: 42649 AN: 152114 Hom.: 6264 Cov.: 33 AF XY: 0.282 AC XY: 20963 AN XY: 74362

African (AFR) AF: 0.242 AC: 10056 AN: 41496

American (AMR) AF: 0.367 AC: 5605 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1501 AN: 5162

South Asian (SAS) AF: 0.182 AC: 875 AN: 4812

European-Finnish (FIN) AF: 0.326 AC: 3448 AN: 10562

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19179 AN: 68006

Other (OTH) AF: 0.297 AC: 627 AN: 2114

Alfa AF: 0.279 Hom.: 771

Bravo AF: 0.287

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.40
PhyloP100		-0.98
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: rs1928984; hg19: chr9-119733957;