1-216073333-AGG-AG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_206933.4(USH2A):c.5573-34del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39957 hom., cov: 0)
  • Exomes 𝑓: 0.71 (366519 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.879

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

USH2A-AS2 (HGNC:40605): (USH2A antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-216073333-AG-A is Benign according to our data. Variant chr1-216073333-AG-A is described in ClinVar as [Benign]. Clinvar id is 1243806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-216073333-AG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.5573-34del		intron_variant		ENST00000307340.8
USH2A-AS2	NR_125992.1	n.136+736del		intron_variant, non_coding_transcript_variant
USH2A-AS2	NR_125993.1	n.136+736del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.5573-34del		intron_variant		1	NM_206933.4	P1
USH2A-AS2	ENST00000446411.5	n.136+736del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109656 AN: 151696 Hom.: 39926 Cov.: 0

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.731

GnomAD3 exomes AF: 0.734 AC: 176766 AN: 240942 Hom.: 65502 AF XY: 0.733 AC XY: 95387 AN XY: 130108

Gnomad AFR exome AF: 0.747

Gnomad AMR exome AF: 0.785

Gnomad ASJ exome AF: 0.726

Gnomad EAS exome AF: 0.954

Gnomad SAS exome AF: 0.771

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.737

GnomAD4 exome AF: 0.708 AC: 1029026 AN: 1453250 Hom.: 366519 Cov.: 0 AF XY: 0.710 AC XY: 513472 AN XY: 722772

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.693

Gnomad4 OTH exome AF: 0.728

GnomAD4 genome AF: 0.723 AC: 109735 AN: 151814 Hom.: 39957 Cov.: 0 AF XY: 0.724 AC XY: 53676 AN XY: 74140

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.730

Alfa AF: 0.706 Hom.: 6932

Bravo AF: 0.734

Asia WGS AF: 0.825 AC: 2869 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Retinitis pigmentosa 39 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Usher syndrome type 2A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs35944387; hg19: chr1-216246675;