1-216073333-AGG-AG

Variant names:

• chr1-216073333-AG-A
• rs35944387
• NM_206933.4:c.5573-34delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_206933.4(USH2A):​c.5573-34delC 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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1243806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206933.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.5573-34delC		intron	N/A	NP_996816.3
	USH2A-AS2	NR_125992.1		n.136+736delG		intron	N/A
	USH2A-AS2	NR_125993.1		n.136+736delG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.5573-34delC		intron	N/A	ENSP00000305941.3
	USH2A	ENST00000674083.1		c.5573-34delC		intron	N/A	ENSP00000501296.1
	USH2A-AS2	ENST00000430890.5	TSL:2	n.78+528delG		intron	N/A

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

GnomAD2 exomes AF: 0.734 AC: 176766 AN: 240942 AF XY: 0.733

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 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

African (AFR) AF: 0.742 AC: 24686 AN: 33260

American (AMR) AF: 0.783 AC: 34485 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 18787 AN: 25932

East Asian (EAS) AF: 0.925 AC: 36478 AN: 39426

South Asian (SAS) AF: 0.771 AC: 65846 AN: 85380

European-Finnish (FIN) AF: 0.640 AC: 33897 AN: 52974

Middle Eastern (MID) AF: 0.755 AC: 4336 AN: 5740

European-Non Finnish (NFE) AF: 0.693 AC: 766749 AN: 1106438

Other (OTH) AF: 0.728 AC: 43762 AN: 60080

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

African (AFR) AF: 0.744 AC: 30782 AN: 41378

American (AMR) AF: 0.762 AC: 11604 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2545 AN: 3462

East Asian (EAS) AF: 0.943 AC: 4845 AN: 5138

South Asian (SAS) AF: 0.782 AC: 3750 AN: 4796

European-Finnish (FIN) AF: 0.638 AC: 6730 AN: 10544

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47076 AN: 67944

Other (OTH) AF: 0.730 AC: 1540 AN: 2110

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

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Retinitis pigmentosa 39 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Usher syndrome type 2A Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88
Mutation Taster		=100/0	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: rs35944387; hg19: chr1-216246675; COSMIC: COSV56329693;