Variant 7-69599681-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015570.4(AUTS2):c.28C>G(p.Leu10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15830332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.28C>G	p.Leu10Val	missense_variant	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10 linkuse as main transcript	c.28C>G	p.Leu10Val	missense_variant	1/19	1	NM_015570.4	P4	Q8WXX7-1
AUTS2	ENST00000406775.6 linkuse as main transcript	c.28C>G	p.Leu10Val	missense_variant	1/18	1			Q8WXX7-2
AUTS2	ENST00000403018.3 linkuse as main transcript	c.28C>G	p.Leu10Val	missense_variant	1/5	1			Q8WXX7-3
AUTS2	ENST00000644939.1 linkuse as main transcript	c.28C>G	p.Leu10Val	missense_variant	1/19			A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1174916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

568156

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2021

Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

.;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L;L;L

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.070

.;N;N;N

REVEL

Benign

0.032

Sift

Pathogenic

0.0

.;D;D;T

Sift4G

Benign

0.75

.;T;T;T

Polyphen

0.36

.;B;B;.

Vest4

0.15, 0.18, 0.11

MutPred

0.28

Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);

MVP

0.10

MPC

2.3

ClinPred

0.62

GERP RS

3.6

Varity_R

0.098

gMVP

0.073

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over