9-116487060-C-G

Variant names:

• chr9-116487060-C-G
• rs7852872
• NM_001365068.1:c.3497+299G>C

Variant summary

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

The NM_001365068.1(ASTN2):​c.3497+299G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,998 control chromosomes in the GnomAD database, including 10,133 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 0.36 (10133 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 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.3497+299G>C		intron	N/A	NP_001351997.1
	ASTN2	NM_001365069.1		c.3485+299G>C		intron	N/A	NP_001351998.1
	ASTN2	NM_014010.5		c.3344+299G>C		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.3497+299G>C		intron	N/A	ENSP00000314038.4
	ASTN2	ENST00000361209.6	TSL:1	c.3344+299G>C		intron	N/A	ENSP00000354504.2
	ASTN2	ENST00000288520.9	TSL:1	c.800+299G>C		intron	N/A	ENSP00000288520.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54129 AN: 151880 Hom.: 10120 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.356 AC: 54173 AN: 151998 Hom.: 10133 Cov.: 32 AF XY: 0.362 AC XY: 26912 AN XY: 74298

African (AFR) AF: 0.270 AC: 11193 AN: 41454

American (AMR) AF: 0.447 AC: 6834 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2630 AN: 5164

South Asian (SAS) AF: 0.516 AC: 2480 AN: 4804

European-Finnish (FIN) AF: 0.395 AC: 4167 AN: 10548

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24717 AN: 67962

Other (OTH) AF: 0.341 AC: 720 AN: 2112

Alfa AF: 0.339 Hom.: 4778

Bravo AF: 0.355

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.40
PhyloP100		-0.18
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: rs7852872; hg19: chr9-119249339; COSMIC: COSV107306304;