7-69599757-C-CCGG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting

The NM_015570(AUTS2):c.114_116dup(p.Gly38dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151516 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Consequence

AUTS2
NM_015570 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.147

Links

AUTS2 (HGNC:14262):

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.0000264 (4/151516) while in subpopulation AFR AF= 0.0000968 (4/41304). AF 95% confidence interval is 0.0000326. There are 0 homozygotes in gnomad. There are 3 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.114_116dup	p.Gly38dup	inframe_insertion	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10 linkuse as main transcript	c.114_116dup	p.Gly38dup	inframe_insertion	1/19	1	NM_015570.4	P4	Q8WXX7-1
AUTS2	ENST00000403018.3 linkuse as main transcript	c.114_116dup	p.Gly38dup	inframe_insertion	1/5	1			Q8WXX7-3
AUTS2	ENST00000406775.6 linkuse as main transcript	c.114_116dup	p.Gly38dup	inframe_insertion	1/18	1			Q8WXX7-2
AUTS2	ENST00000644939.1 linkuse as main transcript	c.114_116dup	p.Gly38dup	inframe_insertion	1/19			A1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1219330

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

595024

show subpopulations

Gnomad4 AFR exome

AF:

0.000124

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:

0.0000200

Gnomad4 OTH exome

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autism spectrum disorder due to AUTS2 deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PerkinElmer Genomics

Mar 19, 2021

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In-frame insertion of 1 amino acid in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over