rs2293508

chr7-70763153-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015570.4(AUTS2):c.1026A>G(p.Pro342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,613,838 control chromosomes in the GnomAD database, including 3,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1085 hom., cov: 32)
  • Exomes 𝑓: 0.048 (2470 hom.)
• Consequence: AUTS2 NM_015570.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-70763153-A-G is Benign according to our data. Variant chr7-70763153-A-G is described in ClinVar as [Benign]. Clinvar id is 1227066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.1026A>G	p.Pro342=	synonymous_variant	7/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.1026A>G	p.Pro342=	synonymous_variant	7/19	1	NM_015570.4	P4

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13938 AN: 151980 Hom.: 1078 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0760

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.0594 AC: 14862 AN: 250036 Hom.: 763 AF XY: 0.0580 AC XY: 7843 AN XY: 135266

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.0747

Gnomad SAS exome AF: 0.0797

Gnomad FIN exome AF: 0.00634

Gnomad NFE exome AF: 0.0412

Gnomad OTH exome AF: 0.0663

GnomAD4 exome AF: 0.0484 AC: 70727 AN: 1461740 Hom.: 2470 Cov.: 32 AF XY: 0.0488 AC XY: 35506 AN XY: 727156

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.0803

Gnomad4 FIN exome AF: 0.00701

Gnomad4 NFE exome AF: 0.0403

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0918 AC: 13963 AN: 152098 Hom.: 1085 Cov.: 32 AF XY: 0.0886 AC XY: 6586 AN XY: 74344

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.00519

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0666 Hom.: 265

Bravo AF: 0.101

Asia WGS AF: 0.0970 AC: 337 AN: 3478

EpiCase AF: 0.0507

EpiControl AF: 0.0489

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.029
Dann	Benign	0.28

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

LitVar

Other links and lift over

dbSNP: rs2293508; hg19: chr7-70228139;