rs767529359

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_015570.4(AUTS2):c.1295C>A(p.Pro432His) variant causes a missense change. The variant allele was found at a frequency of 0.000137 in 1,346,850 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00011 ( 4 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 7.03

Publications

1 publications found

Variant links:

Genes affected

AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]

AUTS2 Gene-Disease associations (from GenCC):

autism spectrum disorder due to AUTS2 deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.085603684).

BP6

Variant 7-70764832-C-A is Benign according to our data. Variant chr7-70764832-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 425414.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00036 (53/147226) while in subpopulation AMR AF = 0.00231 (34/14696). AF 95% confidence interval is 0.0017. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High AC in GnomAd4 at 53 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. 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
	AUTS2	NM_015570.4	MANE Select	c.1295C>A	p.Pro432His	missense	Exon 8 of 19	NP_056385.1
	AUTS2	NM_001127231.3		c.1295C>A	p.Pro432His	missense	Exon 8 of 18	NP_001120703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.1295C>A	p.Pro432His	missense	Exon 8 of 19	ENSP00000344087.4
AUTS2	ENST00000406775.6	TSL:1	c.1295C>A	p.Pro432His	missense	Exon 8 of 18	ENSP00000385263.2
AUTS2	ENST00000644939.1		c.1292C>A	p.Pro431His	missense	Exon 8 of 19	ENSP00000496726.1

Frequencies

GnomAD3 genomes

AF:

0.000360

AC:

AN:

147226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00231

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00101

GnomAD2 exomes

AF:

0.000212

AC:

AN:

170110

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.000300

Gnomad AMR exome

AF:

0.000997

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000211

GnomAD4 exome

AF:

0.000110

AC:

132

AN:

1199624

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

601326

show subpopulations

African (AFR)

AF:

0.000249

AC:

AN:

28124

American (AMR)

AF:

0.000707

AC:

AN:

36772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23814

East Asian (EAS)

AF:

0.00

AC:

AN:

35308

South Asian (SAS)

AF:

0.00

AC:

AN:

76108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49998

Middle Eastern (MID)

AF:

0.000378

AC:

AN:

5286

European-Non Finnish (NFE)

AF:

0.0000907

AC:

AN:

892646

Other (OTH)

AF:

0.000310

AC:

AN:

51568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.630

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000360

AC:

AN:

147226

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

71606

show subpopulations

African (AFR)

AF:

0.000254

AC:

AN:

39400

American (AMR)

AF:

0.00231

AC:

AN:

14696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4932

South Asian (SAS)

AF:

0.00

AC:

AN:

4498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000105

AC:

AN:

66856

Other (OTH)

AF:

0.00101

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.570

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000121

Hom.:

ExAC

AF:

0.0000844

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autism spectrum disorder due to AUTS2 deficiency (1)

AUTS2-related disorder (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.072

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

PhyloP100

7.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.80

MVP

0.29

MPC

1.3

ClinPred

0.11

GERP RS

5.2

Varity_R

0.32

gMVP

0.46

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over