chr9-117039834-G-A

Variant names:

• chr9-117039834-G-A
• rs779863373
• NM_001365068.1:c.1408C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365068.1(ASTN2):​c.1408C>T​(p.His470Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASTN2 NM_001365068.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN2	NM_001365068.1	c.1408C>T	p.His470Tyr	missense_variant	Exon 6 of 23	ENST00000313400.9	NP_001351997.1
ASTN2	NM_001365069.1	c.1408C>T	p.His470Tyr	missense_variant	Exon 6 of 23		NP_001351998.1
ASTN2	NM_014010.5	c.1255C>T	p.His419Tyr	missense_variant	Exon 5 of 22		NP_054729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9	c.1408C>T	p.His470Tyr	missense_variant	Exon 6 of 23	5	NM_001365068.1	ENSP00000314038.4
ASTN2	ENST00000361209.6	c.1255C>T	p.His419Tyr	missense_variant	Exon 5 of 22	1		ENSP00000354504.2
ASTN2	ENST00000361477.8	c.1255C>T	p.His419Tyr	missense_variant	Exon 5 of 23	5		ENSP00000355116.5
ASTN2	ENST00000373986.7	c.589C>T	p.His197Tyr	missense_variant	Exon 4 of 21	2		ENSP00000363098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249932 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135074

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.78
MutPred		0.51		Loss of disorder (P = 0.0688);.;.;
MVP		0.11
MPC		0.27
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.48
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779863373; hg19: chr9-119802113;