rs12404427

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_206933.4(USH2A):c.7506G>A(p.Pro2502Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,613,400 control chromosomes in the GnomAD database, including 6,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 470 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5609 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.03

Publications

9 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:

ENSG00000229242 (HGNC:):

ENSG00000229242 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-215900163-C-T is Benign according to our data. Variant chr1-215900163-C-T is described in ClinVar as Benign. ClinVar VariationId is 48584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 72	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
USH2A	ENST00000307340.8 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 72	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 73			ENSP00000501296.1
ENSG00000229242	ENST00000414995.1 link	n.61-562C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0755

AC:

11471

AN:

151954

Hom.:

470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0537

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0835

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0684

AC:

17142

AN:

250672

AF XY:

0.0676

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0519

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0835

AC:

121987

AN:

1461328

Hom.:

5609

Cov.:

AF XY:

0.0823

AC XY:

59840

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.0809

AC:

2707

AN:

33446

American (AMR)

AF:

0.0916

AC:

4095

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0393

AC:

1027

AN:

26112

East Asian (EAS)

AF:

0.000731

AC:

AN:

39676

South Asian (SAS)

AF:

0.0582

AC:

5022

AN:

86258

European-Finnish (FIN)

AF:

0.0521

AC:

2782

AN:

53378

Middle Eastern (MID)

AF:

0.0331

AC:

191

AN:

5766

European-Non Finnish (NFE)

AF:

0.0915

AC:

101667

AN:

1111652

Other (OTH)

AF:

0.0740

AC:

4467

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5933

11866

17799

23732

29665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3810

7620

11430

15240

19050

<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:

0.0755

AC:

11478

AN:

152072

Hom.:

470

Cov.:

AF XY:

0.0736

AC XY:

5473

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0816

AC:

3387

AN:

41484

American (AMR)

AF:

0.0843

AC:

1286

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5170

South Asian (SAS)

AF:

0.0537

AC:

259

AN:

4822

European-Finnish (FIN)

AF:

0.0502

AC:

530

AN:

10564

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0835

AC:

5674

AN:

67982

Other (OTH)

AF:

0.0621

AC:

131

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

538

1077

1615

2154

2692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0771

Hom.:

872

Bravo

AF:

0.0760

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.0751

EpiControl

AF:

0.0759

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 05, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2013

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Usher syndrome type 2A

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.8

(source)

DANN

Benign

0.81

PhyloP100

-2.0

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

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