chr9-116860159-C-T

Variant names:

• chr9-116860159-C-T
• rs10491574
• NM_001365068.1:c.2040+3424G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):​c.2040+3424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,068 control chromosomes in the GnomAD database, including 2,297 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 (2297 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 7 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

ENSG00000285820 (HGNC:):

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 = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.2040+3424G>A		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.2028+3424G>A		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.1887+3424G>A		intron	N/A	NP_054729.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2040+3424G>A		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.1887+3424G>A		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000361477.8	TSL:5	c.1887+3424G>A		intron	N/A	ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23999 AN: 151950 Hom.: 2303 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.158 AC: 23992 AN: 152068 Hom.: 2297 Cov.: 33 AF XY: 0.160 AC XY: 11927 AN XY: 74346

African (AFR) AF: 0.179 AC: 7424 AN: 41476

American (AMR) AF: 0.243 AC: 3716 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2325 AN: 5138

South Asian (SAS) AF: 0.174 AC: 841 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7927 AN: 67980

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.132 Hom.: 3089

Bravo AF: 0.175

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.19
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: rs10491574; hg19: chr9-119622438;