rs12095085

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_206933.4(USH2A):c.11389+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,609,608 control chromosomes in the GnomAD database, including 13,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1273 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11837 hom. )

Consequence

USH2A
NM_206933.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.449

Publications

4 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 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 39
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

USH2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-215758586-T-A is Benign according to our data. Variant chr1-215758586-T-A is described in ClinVar as Benign. ClinVar VariationId is 48372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.11389+9A>T		intron_variant	Intron 58 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 link	c.11389+9A>T		intron_variant	Intron 58 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1 link	c.11389+9A>T		intron_variant	Intron 58 of 72			ENSP00000501296.1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18727

AN:

151992

Hom.:

1271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.0990

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0452

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.104

AC:

26024

AN:

250720

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.0683

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.123

AC:

179171

AN:

1457498

Hom.:

11837

Cov.:

AF XY:

0.122

AC XY:

88177

AN XY:

725324

show subpopulations

African (AFR)

AF:

0.135

AC:

4511

AN:

33396

American (AMR)

AF:

0.0699

AC:

3126

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3506

AN:

26110

East Asian (EAS)

AF:

0.000177

AC:

AN:

39644

South Asian (SAS)

AF:

0.0545

AC:

4696

AN:

86182

European-Finnish (FIN)

AF:

0.151

AC:

7958

AN:

52692

Middle Eastern (MID)

AF:

0.126

AC:

650

AN:

5152

European-Non Finnish (NFE)

AF:

0.133

AC:

147313

AN:

1109370

Other (OTH)

AF:

0.123

AC:

7404

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7039

14079

21118

28158

35197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5268

10536

15804

21072

26340

<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:

0.123

AC:

18731

AN:

152110

Hom.:

1273

Cov.:

AF XY:

0.122

AC XY:

9048

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.135

AC:

5602

AN:

41490

American (AMR)

AF:

0.0987

AC:

1508

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

470

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.0450

AC:

217

AN:

4824

European-Finnish (FIN)

AF:

0.145

AC:

1539

AN:

10578

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.131

AC:

8930

AN:

67978

Other (OTH)

AF:

0.142

AC:

301

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

859

1719

2578

3438

4297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.104

Hom.:

334

Bravo

AF:

0.120

Asia WGS

AF:

0.0250

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Feb 19, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 18, 2011

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Usher syndrome type 2A

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

(source)

DANN

Benign

0.55

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over