9-116440600-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365068.1(ASTN2):c.3782+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,611,472 control chromosomes in the GnomAD database, including 18,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1324 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16907 hom.)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-116440600-C-A is Benign according to our data. Variant chr9-116440600-C-A is described in ClinVar as [Benign]. Clinvar id is 3060454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.3782+9G>T		intron_variant		ENST00000313400.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.3782+9G>T		intron_variant		5	NM_001365068.1	A2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18828 AN: 152096 Hom.: 1327 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.124 AC: 31058 AN: 250752 Hom.: 2325 AF XY: 0.126 AC XY: 17133 AN XY: 135500

Gnomad AFR exome AF: 0.0676

Gnomad AMR exome AF: 0.0868

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0907

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.147 AC: 214169 AN: 1459258 Hom.: 16907 Cov.: 31 AF XY: 0.146 AC XY: 105977 AN XY: 725916

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.0915

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.124 AC: 18814 AN: 152214 Hom.: 1324 Cov.: 32 AF XY: 0.122 AC XY: 9044 AN XY: 74418

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.130

Alfa AF: 0.135 Hom.: 895

Bravo AF: 0.120

Asia WGS AF: 0.0370 AC: 127 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ASTN2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.015
Dann	Benign	0.37

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: rs74790727; hg19: chr9-119202879;