NM_015570.4:c.1026A>G

Variant names:

• chr7-70763153-A-G
• rs2293508
• NM_015570.4:c.1026A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015570.4(AUTS2):​c.1026A>G​(p.Pro342Pro) 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:3
• Conservation: PhyloP100: -2.27
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BP6: Variant 7-70763153-A-G is Benign according to our data. Variant chr7-70763153-A-G is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.1026A>G	p.Pro342Pro	synonymous_variant	Exon 7 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.1026A>G	p.Pro342Pro	synonymous_variant	Exon 7 of 19	1	NM_015570.4	ENSP00000344087.4

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

GnomAD2 exomes AF: 0.0594 AC: 14862 AN: 250036 AF XY: 0.0580

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 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

African (AFR) AF: 0.211 AC: 7057 AN: 33478

American (AMR) AF: 0.0442 AC: 1979 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2680 AN: 26134

East Asian (EAS) AF: 0.0605 AC: 2403 AN: 39700

South Asian (SAS) AF: 0.0803 AC: 6923 AN: 86248

European-Finnish (FIN) AF: 0.00701 AC: 374 AN: 53370

Middle Eastern (MID) AF: 0.122 AC: 706 AN: 5768

European-Non Finnish (NFE) AF: 0.0403 AC: 44763 AN: 1111934

Other (OTH) AF: 0.0636 AC: 3842 AN: 60384

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

African (AFR) AF: 0.212 AC: 8812 AN: 41470

American (AMR) AF: 0.0632 AC: 966 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.0761 AC: 392 AN: 5148

South Asian (SAS) AF: 0.0774 AC: 372 AN: 4804

European-Finnish (FIN) AF: 0.00519 AC: 55 AN: 10604

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.0389 AC: 2642 AN: 68004

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0530 Hom.: 535

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.029
DANN	Benign	0.28
PhyloP100		-2.3
PromoterAI		-0.00040	Neutral
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293508; hg19: chr7-70228139;