9-117017531-C-T

Variant names:

• chr9-117017531-C-T
• rs2418446
• NM_001365068.1:c.1424-9272G>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.1424-9272G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,022 control chromosomes in the GnomAD database, including 34,427 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 0.66 (34427 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 2 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 (AMR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1424-9272G>A		intron_variant	Intron 6 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1424-9272G>A		intron_variant	Intron 6 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1271-9272G>A		intron_variant	Intron 5 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1424-9272G>A		intron_variant	Intron 6 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1271-9272G>A		intron_variant	Intron 5 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1271-9272G>A		intron_variant	Intron 5 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.605-9272G>A		intron_variant	Intron 4 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100814 AN: 151904 Hom.: 34432 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.663 AC: 100848 AN: 152022 Hom.: 34427 Cov.: 33 AF XY: 0.664 AC XY: 49358 AN XY: 74294

African (AFR) AF: 0.503 AC: 20837 AN: 41454

American (AMR) AF: 0.758 AC: 11593 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2316 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2693 AN: 5136

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4820

European-Finnish (FIN) AF: 0.736 AC: 7778 AN: 10570

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.738 AC: 50145 AN: 67976

Other (OTH) AF: 0.662 AC: 1396 AN: 2108

Alfa AF: 0.711 Hom.: 162136

Bravo AF: 0.655

Asia WGS AF: 0.567 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.14
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: rs2418446; hg19: chr9-119779810;