9-116728195-T-C

Variant names:

• chr9-116728195-T-C
• rs10491577
• NM_001365068.1:c.2626+797A>G

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+797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,162 control chromosomes in the GnomAD database, including 742 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 0.093 (742 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2626+797A>G		intron_variant	Intron 15 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.2614+797A>G		intron_variant	Intron 15 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.2473+797A>G		intron_variant	Intron 14 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.2626+797A>G		intron_variant	Intron 15 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.2473+797A>G		intron_variant	Intron 14 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.2473+797A>G		intron_variant	Intron 14 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.1795+797A>G		intron_variant	Intron 13 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14113 AN: 152044 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0927 AC: 14107 AN: 152162 Hom.: 742 Cov.: 32 AF XY: 0.0934 AC XY: 6947 AN XY: 74372

African (AFR) AF: 0.0564 AC: 2342 AN: 41524

American (AMR) AF: 0.0613 AC: 937 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3466

East Asian (EAS) AF: 0.177 AC: 914 AN: 5174

South Asian (SAS) AF: 0.0785 AC: 377 AN: 4800

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7440 AN: 67994

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.0999 Hom.: 903

Bravo AF: 0.0872

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.26
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: rs10491577; hg19: chr9-119490474;