rs16934284

Variant names:

• chr9-117077049-T-C
• rs16934284
• NM_001365068.1:c.1276+18995A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001365068.1(ASTN2):​c.1276+18995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,056 control chromosomes in the GnomAD database, including 2,607 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 0.16 (2607 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1276+18995A>G		intron_variant	Intron 5 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1276+18995A>G		intron_variant	Intron 5 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1123+18995A>G		intron_variant	Intron 4 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1276+18995A>G		intron_variant	Intron 5 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1123+18995A>G		intron_variant	Intron 4 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1123+18995A>G		intron_variant	Intron 4 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.457+18995A>G		intron_variant	Intron 3 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24977 AN: 151938 Hom.: 2602 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.164 AC: 24993 AN: 152056 Hom.: 2607 Cov.: 32 AF XY: 0.165 AC XY: 12251 AN XY: 74318

African (AFR) AF: 0.273 AC: 11328 AN: 41454

American (AMR) AF: 0.0893 AC: 1365 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1448 AN: 5130

South Asian (SAS) AF: 0.173 AC: 833 AN: 4822

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10572

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7905 AN: 68008

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.136 Hom.: 5202

Bravo AF: 0.169

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.67
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: rs16934284; hg19: chr9-119839328;