7-69598633-A-AGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015570.4(AUTS2):c.-1003_-1001dup 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.05

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.-1003_-1001dup		5_prime_UTR_variant	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.-1003_-1001dup		5_prime_UTR_variant	1/19	1	NM_015570.4	P4
AUTS2	ENST00000644939.1	c.-1003_-1001dup		5_prime_UTR_variant	1/19			A1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2587 AN: 128144 Hom.: 71 Cov.: 30

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: 23 AN: 20604 Hom.: 0 Cov.: 0 AF XY: 0.000837 AC XY: 11 AN XY: 13144

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000420

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000378

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.0203 AC: 2601 AN: 128176 Hom.: 72 Cov.: 30 AF XY: 0.0198 AC XY: 1238 AN XY: 62654

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.00985

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00132

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000135

Gnomad4 OTH AF: 0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 17, 2020

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs572172462; hg19: chr7-69063619;