rs3761845

Variant names:

• chr9-117008201-C-T
• rs3761845
• NM_001365068.1:c.1482G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-117008201-C-T
• chr9-117008201-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001365068.1(ASTN2):​c.1482G>A​(p.Pro494Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,609,010 control chromosomes in the GnomAD database, including 255,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (19425 hom., cov: 32)
  • Exomes 𝑓: 0.56 (235946 hom.)
• Consequence: ASTN2 NM_001365068.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.892
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-117008201-C-T is Benign according to our data. Variant chr9-117008201-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.892 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.1482G>A	p.Pro494Pro	synonymous	Exon 7 of 23	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.1482G>A	p.Pro494Pro	synonymous	Exon 7 of 23	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.1329G>A	p.Pro443Pro	synonymous	Exon 6 of 22	NP_054729.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.1482G>A	p.Pro494Pro	synonymous	Exon 7 of 23	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.1329G>A	p.Pro443Pro	synonymous	Exon 6 of 22	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000882685.1		c.1479G>A	p.Pro493Pro	synonymous	Exon 7 of 23	ENSP00000552744.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71395 AN: 151880 Hom.: 19424 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.559 AC: 138218 AN: 247390 AF XY: 0.555

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.712

Gnomad ASJ exome AF: 0.495

Gnomad EAS exome AF: 0.747

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.563 AC: 820377 AN: 1457012 Hom.: 235946 Cov.: 50 AF XY: 0.560 AC XY: 406116 AN XY: 724672

African (AFR) AF: 0.163 AC: 5443 AN: 33388

American (AMR) AF: 0.704 AC: 31068 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 12929 AN: 26014

East Asian (EAS) AF: 0.759 AC: 29874 AN: 39358

South Asian (SAS) AF: 0.495 AC: 42245 AN: 85282

European-Finnish (FIN) AF: 0.562 AC: 30000 AN: 53350

Middle Eastern (MID) AF: 0.448 AC: 2581 AN: 5756

European-Non Finnish (NFE) AF: 0.571 AC: 633230 AN: 1109548

Other (OTH) AF: 0.548 AC: 33007 AN: 60204

GnomAD4 genome AF: 0.470 AC: 71416 AN: 151998 Hom.: 19425 Cov.: 32 AF XY: 0.474 AC XY: 35256 AN XY: 74302

African (AFR) AF: 0.184 AC: 7649 AN: 41458

American (AMR) AF: 0.621 AC: 9498 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3470

East Asian (EAS) AF: 0.744 AC: 3831 AN: 5146

South Asian (SAS) AF: 0.505 AC: 2423 AN: 4798

European-Finnish (FIN) AF: 0.549 AC: 5807 AN: 10568

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38722 AN: 67964

Other (OTH) AF: 0.516 AC: 1086 AN: 2106

Alfa AF: 0.526 Hom.: 35396

Bravo AF: 0.468

Asia WGS AF: 0.572 AC: 1989 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		-0.89
Mutation Taster		=292/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3761845; hg19: chr9-119770480; COSMIC: COSV108101362;