9-116487369-C-G

Variant names:

• chr9-116487369-C-G
• rs765621808
• NM_001365068.1:c.3487G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365068.1(ASTN2):​c.3487G>C​(p.Gly1163Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1163S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASTN2 NM_001365068.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 1 publications found

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]

ASTN2 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31032866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	NM_001365068.1	MANE Select	c.3487G>C	p.Gly1163Arg	missense	Exon 20 of 23	NP_001351997.1	O75129-1
	ASTN2	NM_001365069.1		c.3475G>C	p.Gly1159Arg	missense	Exon 20 of 23	NP_001351998.1	O75129-3
	ASTN2	NM_014010.5		c.3334G>C	p.Gly1112Arg	missense	Exon 19 of 22	NP_054729.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.3487G>C	p.Gly1163Arg	missense	Exon 20 of 23	ENSP00000314038.4	O75129-1
	ASTN2	ENST00000361209.6	TSL:1	c.3334G>C	p.Gly1112Arg	missense	Exon 19 of 22	ENSP00000354504.2	O75129-2
	ASTN2	ENST00000288520.9	TSL:1	c.790G>C	p.Gly264Arg	missense	Exon 5 of 8	ENSP00000288520.5	O75129-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Benign	0.046	D
Sift4G	Benign	0.067	T
Polyphen		0.98	D
Vest4		0.67
MutPred		0.39		Gain of ubiquitination at K1166 (P = 0.0797)
MVP		0.068
MPC		0.28
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.57
gMVP		0.67
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs765621808; hg19: chr9-119249648;