9-116713991-T-C

Variant names:

• chr9-116713991-T-C
• rs719535
• NM_001365068.1:c.2806+11780A>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.2806+11780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,056 control chromosomes in the GnomAD database, including 41,212 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 0.73 (41212 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2806+11780A>G		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.2794+11780A>G		intron_variant	Intron 16 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.2653+11780A>G		intron_variant	Intron 15 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.2806+11780A>G		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.2653+11780A>G		intron_variant	Intron 15 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.2653+11780A>G		intron_variant	Intron 15 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.1975+11780A>G		intron_variant	Intron 14 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111346 AN: 151938 Hom.: 41176 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.733 AC: 111437 AN: 152056 Hom.: 41212 Cov.: 32 AF XY: 0.725 AC XY: 53925 AN XY: 74330

African (AFR) AF: 0.754 AC: 31247 AN: 41468

American (AMR) AF: 0.785 AC: 11983 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2652 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2331 AN: 5156

South Asian (SAS) AF: 0.480 AC: 2311 AN: 4816

European-Finnish (FIN) AF: 0.691 AC: 7305 AN: 10576

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51029 AN: 67982

Other (OTH) AF: 0.767 AC: 1618 AN: 2110

Alfa AF: 0.746 Hom.: 176354

Bravo AF: 0.747

Asia WGS AF: 0.548 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.82
PhyloP100		-0.13
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: rs719535; hg19: chr9-119476270;