rs1372328

chr9-116722249-C-T

Variant summary

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

The NM_001365068.1(ASTN2):c.2806+3522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,268 control chromosomes in the GnomAD database, including 14,236 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 0.42 (14236 hom., cov: 33)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.2806+3522G>A		intron_variant		ENST00000313400.9
ASTN2	NM_001365069.1	c.2794+3522G>A		intron_variant
ASTN2	NM_014010.5	c.2653+3522G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.2806+3522G>A		intron_variant		5	NM_001365068.1	A2
ASTN2	ENST00000361209.6	c.2653+3522G>A		intron_variant		1		P2
ASTN2	ENST00000361477.8	c.2653+3522G>A		intron_variant		5		A2
ASTN2	ENST00000373986.7	c.1975+3522G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64149 AN: 151154 Hom.: 14232 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.424 AC: 64187 AN: 151268 Hom.: 14236 Cov.: 33 AF XY: 0.426 AC XY: 31489 AN XY: 73928

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.454

Alfa AF: 0.460 Hom.: 21761

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.3
Dann	Benign	0.66

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: rs1372328; hg19: chr9-119484528;