7-69599651-A-G

Variant names:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -16 ACMG points: 0P and 16B. BA1BP4_StrongBP6_Strong

The NM_015570.4(AUTS2):c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0846 (AC=109,796) in the gnomAD database across 1,297,190 control chromosomes, including 5,804 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.258. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1768 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4036 hom. )

Consequence

AUTS2
NM_015570.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

Publications

8 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015570.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2577 — exceeds 5%% threshold (BA1 applied)

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AUTS2	NM_015570.4	MANE Select	c.-3A>G	5_prime_UTR	Exon 1 of 19	NP_056385.1	Q8WXX7-1
AUTS2	NM_001127231.3		c.-3A>G	5_prime_UTR	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
AUTS2	NM_001127232.3		c.-3A>G	5_prime_UTR	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.-3A>G	5_prime_UTR	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
AUTS2	ENST00000406775.6	TSL:1	c.-3A>G	5_prime_UTR	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
AUTS2	ENST00000403018.3	TSL:1	c.-3A>G	5_prime_UTR	Exon 1 of 5	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19102

AN:

151634

Hom.:

1760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0177

Gnomad AMR

AF:

0.0760

Gnomad ASJ

AF:

0.0820

Gnomad EAS

AF:

0.0781

Gnomad SAS

AF:

0.0850

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0757

Gnomad OTH

AF:

0.106

GnomAD2 exomes

AF:

0.0568

AC:

497

AN:

8750

AF XY:

0.0576

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0420

Gnomad ASJ exome

AF:

0.0694

Gnomad EAS exome

AF:

0.0286

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0666

Gnomad OTH exome

AF:

0.0672

GnomAD4 exome

AF:

0.0791

AC:

90660

AN:

1145448

Hom.:

4036

Cov.:

AF XY:

0.0790

AC XY:

43457

AN XY:

550410

show subpopulations

African (AFR)

AF:

0.263

AC:

6091

AN:

23138

American (AMR)

AF:

0.0766

AC:

678

AN:

8850

Ashkenazi Jewish (ASJ)

AF:

0.0827

AC:

1243

AN:

15022

East Asian (EAS)

AF:

0.0552

AC:

1484

AN:

26900

South Asian (SAS)

AF:

0.0799

AC:

2489

AN:

31150

European-Finnish (FIN)

AF:

0.0575

AC:

1854

AN:

32234

Middle Eastern (MID)

AF:

0.0766

AC:

236

AN:

3082

European-Non Finnish (NFE)

AF:

0.0755

AC:

72407

AN:

958832

Other (OTH)

AF:

0.0904

AC:

4178

AN:

46240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4512

9024

13535

18047

22559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3082

6164

9246

12328

15410

<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:

0.126

AC:

19136

AN:

151742

Hom.:

1768

Cov.:

AF XY:

0.124

AC XY:

9223

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.262

AC:

10842

AN:

41424

American (AMR)

AF:

0.0760

AC:

1163

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0820

AC:

284

AN:

3462

East Asian (EAS)

AF:

0.0779

AC:

395

AN:

5068

South Asian (SAS)

AF:

0.0843

AC:

406

AN:

4816

European-Finnish (FIN)

AF:

0.0616

AC:

648

AN:

10524

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0757

AC:

5137

AN:

67852

Other (OTH)

AF:

0.107

AC:

224

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

824

1647

2471

3294

4118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0916

Hom.:

915

Bravo

AF:

0.134

Asia WGS

AF:

0.101

AC:

351

AN:

3476

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0507

AC:

5762

AN:

113658

Turkish Variome

AF:

0.0784

AC:

121

AN:

1544

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0782

AC:

701

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.119

AC:

279

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.0

PromoterAI

0.043

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over