NM_001365068.1:c.1277-10470G>C

Variant names:

• chr9-117050435-C-G
• rs10513281
• NM_001365068.1:c.1277-10470G>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.1277-10470G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,998 control chromosomes in the GnomAD database, including 1,968 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 (1968 hom., cov: 31)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1277-10470G>C		intron_variant	Intron 5 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1277-10470G>C		intron_variant	Intron 5 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.1124-10470G>C		intron_variant	Intron 4 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1277-10470G>C		intron_variant	Intron 5 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1124-10470G>C		intron_variant	Intron 4 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1124-10470G>C		intron_variant	Intron 4 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.458-10470G>C		intron_variant	Intron 3 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23528 AN: 151880 Hom.: 1966 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.155 AC: 23545 AN: 151998 Hom.: 1968 Cov.: 31 AF XY: 0.150 AC XY: 11174 AN XY: 74300

African (AFR) AF: 0.180 AC: 7483 AN: 41478

American (AMR) AF: 0.129 AC: 1967 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3472

East Asian (EAS) AF: 0.000972 AC: 5 AN: 5142

South Asian (SAS) AF: 0.0441 AC: 212 AN: 4808

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11404 AN: 67934

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.153 Hom.: 237

Bravo AF: 0.157

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.67
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: rs10513281; hg19: chr9-119812714;