chr9-117008201-C-G

Position:

• chr9-117008201-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001365068.1(ASTN2):​c.1482G>C​(p.Pro494Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ASTN2 NM_001365068.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.892 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1482G>C	p.Pro494Pro	synonymous_variant	7/23	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1482G>C	p.Pro494Pro	synonymous_variant	7/23		NP_001351998.1
ASTN2	NM_014010.5	c.1329G>C	p.Pro443Pro	synonymous_variant	6/22		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1482G>C	p.Pro494Pro	synonymous_variant	7/23	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1329G>C	p.Pro443Pro	synonymous_variant	6/22	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1329G>C	p.Pro443Pro	synonymous_variant	6/23	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.663G>C	p.Pro221Pro	synonymous_variant	5/21	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458972 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 725682

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.28
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3761845; hg19: chr9-119770480;