rs7028544

Positions:

• chr9-116728293-A-G

Variant summary

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

The NM_001365068.1(ASTN2):​c.2626+699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,030 control chromosomes in the GnomAD database, including 9,244 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 0.33 (9244 hom., cov: 31)
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.2626+699T>C		intron_variant		ENST00000313400.9
ASTN2	NM_001365069.1	c.2614+699T>C		intron_variant
ASTN2	NM_014010.5	c.2473+699T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.2626+699T>C		intron_variant		5	NM_001365068.1	A2
ASTN2	ENST00000361209.6	c.2473+699T>C		intron_variant		1		P2
ASTN2	ENST00000361477.8	c.2473+699T>C		intron_variant		5		A2
ASTN2	ENST00000373986.7	c.1795+699T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50204 AN: 151912 Hom.: 9244 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.330 AC: 50212 AN: 152030 Hom.: 9244 Cov.: 31 AF XY: 0.333 AC XY: 24741 AN XY: 74280

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.340

Alfa AF: 0.374 Hom.: 15645

Bravo AF: 0.306

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.51

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: rs7028544; hg19: chr9-119490572;