rs56110889

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_206933.4(USH2A):c.5013C>A(p.Gly1671Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,611,682 control chromosomes in the GnomAD database, including 23,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2188 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21000 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.171

Publications

14 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

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 1-216084852-G-T is Benign according to our data. Variant chr1-216084852-G-T is described in ClinVar as Benign. ClinVar VariationId is 48527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.171 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.5013C>A	p.Gly1671Gly	synonymous_variant	Exon 25 of 72	ENST00000307340.8	NP_996816.3	O75445-1
USH2A-AS2	NR_125992.1 link	n.266-1870G>T		intron_variant	Intron 2 of 2
USH2A-AS2	NR_125993.1 link	n.137-1870G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 link	c.5013C>A	p.Gly1671Gly	synonymous_variant	Exon 25 of 72	1	NM_206933.4	ENSP00000305941.3		O75445-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24671

AN:

151924

Hom.:

2189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0584

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.133

AC:

33426

AN:

250622

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0944

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.163

AC:

237752

AN:

1459640

Hom.:

21000

Cov.:

AF XY:

0.161

AC XY:

116997

AN XY:

726212

show subpopulations

African (AFR)

AF:

0.204

AC:

6826

AN:

33390

American (AMR)

AF:

0.0967

AC:

4312

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4379

AN:

26102

East Asian (EAS)

AF:

0.000353

AC:

AN:

39674

South Asian (SAS)

AF:

0.0788

AC:

6800

AN:

86240

European-Finnish (FIN)

AF:

0.111

AC:

5912

AN:

53326

Middle Eastern (MID)

AF:

0.130

AC:

750

AN:

5754

European-Non Finnish (NFE)

AF:

0.180

AC:

199469

AN:

1110254

Other (OTH)

AF:

0.154

AC:

9290

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

10518

21036

31554

42072

52590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6864

13728

20592

27456

34320

<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:

0.162

AC:

24671

AN:

152042

Hom.:

2188

Cov.:

AF XY:

0.156

AC XY:

11608

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.193

AC:

8024

AN:

41468

American (AMR)

AF:

0.135

AC:

2059

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

556

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.0576

AC:

278

AN:

4828

European-Finnish (FIN)

AF:

0.102

AC:

1073

AN:

10566

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12228

AN:

67964

Other (OTH)

AF:

0.144

AC:

305

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1048

2095

3143

4190

5238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.177

Hom.:

997

Bravo

AF:

0.167

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 06, 2015

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

- -

Oct 30, 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. -

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

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

-0.45

CADD

Benign

6.8

(source)

DANN

Benign

0.77

PhyloP100

0.17

Mutation Taster

=99/1

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