Genetic Variant AUTS2:c.-1003_-1001dupGGC (chr7-69598633-A-AGCG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_015570.4(AUTS2):c.-1003_-1001dupGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 148,780 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 72 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

Publications

0 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), Orphanet, G2P
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-69598633-A-AGCG is Benign according to our data. Variant chr7-69598633-A-AGCG is described in ClinVar as Benign. ClinVar VariationId is 1290296.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

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.-1003_-1001dupGGC	5_prime_UTR	Exon 1 of 19	NP_056385.1	Q8WXX7-1
AUTS2	NM_001127231.3		c.-1003_-1001dupGGC	5_prime_UTR	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
AUTS2	NM_001127232.3		c.-1003_-1001dupGGC	5_prime_UTR	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.-1003_-1001dupGGC		5_prime_UTR	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000644939.1		c.-1003_-1001dupGGC		5_prime_UTR	Exon 1 of 19	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

2587

AN:

128144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0714

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00985

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00132

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0120

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.0126

GnomAD4 exome

AF:

0.00112

AC:

AN:

20604

Hom.:

Cov.:

AF XY:

0.000837

AC XY:

AN XY:

13144

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

144

American (AMR)

AF:

0.0143

AC:

AN:

140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

244

East Asian (EAS)

AF:

0.00

AC:

AN:

302

South Asian (SAS)

AF:

0.000420

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000378

AC:

AN:

13234

Other (OTH)

AF:

0.00229

AC:

AN:

874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0203

AC:

2601

AN:

128176

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1238

AN XY:

62654

show subpopulations

African (AFR)

AF:

0.0717

AC:

2434

AN:

33950

American (AMR)

AF:

0.00985

AC:

131

AN:

13306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3110

East Asian (EAS)

AF:

0.00

AC:

AN:

4122

South Asian (SAS)

AF:

0.00132

AC:

AN:

3780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8012

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

59236

Other (OTH)

AF:

0.0125

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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