rs10817934

Variant names:

• chr9-116787772-C-T
• rs10817934
• NM_001365068.1:c.2396+17860G>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.2396+17860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,038 control chromosomes in the GnomAD database, including 4,544 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 0.22 (4544 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.2396+17860G>A		intron_variant	Intron 13 of 22	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.2384+17860G>A		intron_variant	Intron 13 of 22		NP_001351998.1
ASTN2	NM_014010.5	c.2243+17860G>A		intron_variant	Intron 12 of 21		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.2396+17860G>A		intron_variant	Intron 13 of 22	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.2243+17860G>A		intron_variant	Intron 12 of 21	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.2243+17860G>A		intron_variant	Intron 12 of 22	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.1565+17860G>A		intron_variant	Intron 11 of 20	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34009 AN: 151920 Hom.: 4544 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.224 AC: 34005 AN: 152038 Hom.: 4544 Cov.: 32 AF XY: 0.223 AC XY: 16581 AN XY: 74308

African (AFR) AF: 0.0739 AC: 3065 AN: 41490

American (AMR) AF: 0.241 AC: 3676 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 977 AN: 3472

East Asian (EAS) AF: 0.103 AC: 532 AN: 5170

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3354 AN: 10532

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20361 AN: 67968

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.275 Hom.: 16714

Bravo AF: 0.209

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.22
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10817934; hg19: chr9-119550051;