Genetic Variant USH2A:c.5573-34delC (chr1-216073333-AG-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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 (★★). The gene USH2A is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.72 ( 39957 hom., cov: 0)

Exomes 𝑓: 0.71 ( 366519 hom. )

Consequence

USH2A
NM_206933.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.879

Publications

10 publications found

Variant links:

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 links:

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

USH2A-AS2 links:

Genome browser will be placed here

ACMG classification

Specifications for USH2A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USH2A	NM_206933.4	MANE Select	c.5573-34delC	intron	N/A	NP_996816.3	O75445-1
USH2A-AS2	NR_125992.1		n.136+736delG	intron	N/A
USH2A-AS2	NR_125993.1		n.136+736delG	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USH2A	ENST00000307340.8	TSL:1 MANE Select	c.5573-34delC	intron	N/A	ENSP00000305941.3	O75445-1
USH2A	ENST00000674083.1		c.5573-34delC	intron	N/A	ENSP00000501296.1	O75445-3
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.710

AC XY:

513472

AN XY:

722772

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

15683

31365

47048

62730

78413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19584

39168

58752

78336

97920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.723

AC:

109735

AN:

151814

Hom.:

39957

Cov.:

AF XY:

0.724

AC XY:

53676

AN XY:

74140

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1522

3043

4565

6086

7608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.706

Hom.:

6932

Bravo

AF:

0.734

Asia WGS

AF:

0.825

AC:

2869

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa 39 (1)

Usher syndrome type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over