NM_001365068.1:c.443-6582T>C

Variant names:

• chr9-117298095-A-G
• rs2416594
• NM_001365068.1:c.443-6582T>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.443-6582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,046 control chromosomes in the GnomAD database, including 14,350 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 0.42 (14350 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.443-6582T>C		intron_variant	Intron 1 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.443-6582T>C		intron_variant	Intron 1 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.443-6582T>C		intron_variant	Intron 1 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.443-6582T>C		intron_variant	Intron 1 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.443-6582T>C		intron_variant	Intron 1 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.443-6582T>C		intron_variant	Intron 1 of 22	5		ENSP00000355116.5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63417 AN: 151928 Hom.: 14357 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.417 AC: 63422 AN: 152046 Hom.: 14350 Cov.: 32 AF XY: 0.426 AC XY: 31681 AN XY: 74342

African (AFR) AF: 0.246 AC: 10216 AN: 41474

American (AMR) AF: 0.460 AC: 7022 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1597 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2165 AN: 5160

South Asian (SAS) AF: 0.609 AC: 2938 AN: 4824

European-Finnish (FIN) AF: 0.574 AC: 6069 AN: 10572

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32054 AN: 67946

Other (OTH) AF: 0.409 AC: 866 AN: 2116

Alfa AF: 0.458 Hom.: 16265

Bravo AF: 0.397

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.35
PhyloP100		-0.91
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: rs2416594; hg19: chr9-120060374;