NM_001365068.1:c.1423+2514G>A

Variant names:

• chr9-117037305-C-T
• rs9697192
• NM_001365068.1:c.1423+2514G>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.1423+2514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 150,120 control chromosomes in the GnomAD database, including 1,979 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 0.15 (1979 hom., cov: 31)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1423+2514G>A		intron_variant	Intron 6 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1423+2514G>A		intron_variant	Intron 6 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1270+2514G>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.1423+2514G>A		intron_variant	Intron 6 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1270+2514G>A		intron_variant	Intron 5 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1270+2514G>A		intron_variant	Intron 5 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.604+2514G>A		intron_variant	Intron 4 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22305 AN: 150002 Hom.: 1975 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0159

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.149 AC: 22343 AN: 150120 Hom.: 1979 Cov.: 31 AF XY: 0.144 AC XY: 10560 AN XY: 73238

African (AFR) AF: 0.250 AC: 10299 AN: 41216

American (AMR) AF: 0.0968 AC: 1455 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 514 AN: 3428

East Asian (EAS) AF: 0.0160 AC: 75 AN: 4692

South Asian (SAS) AF: 0.164 AC: 760 AN: 4624

European-Finnish (FIN) AF: 0.0584 AC: 605 AN: 10358

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8175 AN: 67488

Other (OTH) AF: 0.149 AC: 311 AN: 2084

Alfa AF: 0.127 Hom.: 4374

Bravo AF: 0.153

Asia WGS AF: 0.0970 AC: 339 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-2.3
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: rs9697192; hg19: chr9-119799584;