9-117309269-G-A

Variant names:

• chr9-117309269-G-A
• rs1572306
• NM_001365068.1:c.443-17756C>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.443-17756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,124 control chromosomes in the GnomAD database, including 2,736 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 0.17 (2736 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.443-17756C>T		intron_variant	Intron 1 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.443-17756C>T		intron_variant	Intron 1 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.443-17756C>T		intron_variant	Intron 1 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.443-17756C>T		intron_variant	Intron 1 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.443-17756C>T		intron_variant	Intron 1 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.443-17756C>T		intron_variant	Intron 1 of 22	5		ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25969 AN: 152006 Hom.: 2735 Cov.: 33

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.171 AC: 25964 AN: 152124 Hom.: 2736 Cov.: 33 AF XY: 0.178 AC XY: 13266 AN XY: 74358

African (AFR) AF: 0.0458 AC: 1900 AN: 41528

American (AMR) AF: 0.233 AC: 3555 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3472

East Asian (EAS) AF: 0.189 AC: 975 AN: 5156

South Asian (SAS) AF: 0.238 AC: 1145 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3130 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14111 AN: 67992

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.191 Hom.: 4343

Bravo AF: 0.156

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.62
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: rs1572306; hg19: chr9-120071548;