rs6478282

Variant names:

• chr9-117162816-G-T
• rs6478282
• NM_001365068.1:c.1016-21338C>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.1016-21338C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,892 control chromosomes in the GnomAD database, including 6,783 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 0.29 (6783 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1016-21338C>A		intron_variant	Intron 3 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1016-21338C>A		intron_variant	Intron 3 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1015+51542C>A		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.1016-21338C>A		intron_variant	Intron 3 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1015+51542C>A		intron_variant	Intron 3 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1015+51542C>A		intron_variant	Intron 3 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.197-21338C>A		intron_variant	Intron 1 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44744 AN: 151774 Hom.: 6774 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.295 AC: 44786 AN: 151892 Hom.: 6783 Cov.: 32 AF XY: 0.298 AC XY: 22140 AN XY: 74244

African (AFR) AF: 0.349 AC: 14463 AN: 41420

American (AMR) AF: 0.254 AC: 3877 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1373 AN: 5132

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4818

European-Finnish (FIN) AF: 0.355 AC: 3755 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18381 AN: 67896

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.273 Hom.: 16498

Bravo AF: 0.288

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.70
PhyloP100		1.3
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: rs6478282; hg19: chr9-119925095;