Genetic Variant AUTS2:p.Arg27Trp (chr7-69599732-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_015570.4(AUTS2):c.79C>T(p.Arg27Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000852 in 1,173,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.217

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), G2P, Orphanet
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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30025923).

BP6

Variant 7-69599732-C-T is Benign according to our data. Variant chr7-69599732-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2704710.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.79C>T	p.Arg27Trp	missense_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10 link	c.79C>T	p.Arg27Trp	missense_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.52e-7

AC:

AN:

1173664

Hom.:

Cov.:

AF XY:

0.00000176

AC XY:

AN XY:

567704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23268

American (AMR)

AF:

0.00

AC:

AN:

8892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15342

East Asian (EAS)

AF:

0.00

AC:

AN:

27108

South Asian (SAS)

AF:

0.00

AC:

AN:

36270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3228

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

975296

Other (OTH)

AF:

0.00

AC:

AN:

47588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

.;.;T;.

Eigen

Benign

0.018

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.85

T;D;T;T

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

.;N;N;N

PhyloP100

0.22

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-1.2

.;N;N;D

REVEL

Benign

0.058

Sift

Uncertain

0.0010

.;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;D

Polyphen

0.95

.;P;P;.

Vest4

0.20, 0.27, 0.20

MutPred

0.26

Loss of methylation at R27 (P = 0.0099);Loss of methylation at R27 (P = 0.0099);Loss of methylation at R27 (P = 0.0099);Loss of methylation at R27 (P = 0.0099);

MVP

0.14

MPC

2.6

ClinPred

0.68

GERP RS

1.6

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.15

gMVP

0.12

Mutation Taster

=89/11

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over