rs2050274

chr9-117033417-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365068.1(ASTN2):c.1423+6402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,030 control chromosomes in the GnomAD database, including 41,590 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 0.74 (41590 hom., cov: 32)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.1423+6402A>G		intron_variant		ENST00000313400.9
ASTN2	NM_001365069.1	c.1423+6402A>G		intron_variant
ASTN2	NM_014010.5	c.1270+6402A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.1423+6402A>G		intron_variant		5	NM_001365068.1	A2
ASTN2	ENST00000361209.6	c.1270+6402A>G		intron_variant		1		P2
ASTN2	ENST00000361477.8	c.1270+6402A>G		intron_variant		5		A2
ASTN2	ENST00000373986.7	c.604+6402A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112191 AN: 151912 Hom.: 41543 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.739 AC: 112296 AN: 152030 Hom.: 41590 Cov.: 32 AF XY: 0.738 AC XY: 54848 AN XY: 74306

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.769

Alfa AF: 0.722 Hom.: 6236

Bravo AF: 0.744

Asia WGS AF: 0.830 AC: 2884 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.27
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs2050274; hg19: chr9-119795696;