rs10491577

Positions:

• chr9-116728195-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.2626+797A>G		intron_variant		ENST00000313400.9
ASTN2	NM_001365069.1	c.2614+797A>G		intron_variant
ASTN2	NM_014010.5	c.2473+797A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.2626+797A>G		intron_variant		5	NM_001365068.1	A2
ASTN2	ENST00000361209.6	c.2473+797A>G		intron_variant		1		P2
ASTN2	ENST00000361477.8	c.2473+797A>G		intron_variant		5		A2
ASTN2	ENST00000373986.7	c.1795+797A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0978

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.101 Hom.: 688

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10491577; hg19: chr9-119490474;