1-215674720-C-T

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.13191G>A(p.Glu4397Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,934 control chromosomes in the GnomAD database, including 32,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2357 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29876 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.299

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 1-215674720-C-T is Benign according to our data. Variant chr1-215674720-C-T is described in ClinVar as Benign. ClinVar VariationId is 48413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.299 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.13191G>A	p.Glu4397Glu	synonymous_variant	Exon 63 of 72	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 link	c.13191G>A	p.Glu4397Glu	synonymous_variant	Exon 63 of 72	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1 link	c.13191G>A	p.Glu4397Glu	synonymous_variant	Exon 63 of 73			ENSP00000501296.1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24119

AN:

152006

Hom.:

2361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.203

AC:

50858

AN:

250696

AF XY:

0.209

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.196

AC:

286883

AN:

1461810

Hom.:

29876

Cov.:

AF XY:

0.199

AC XY:

145013

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0508

AC:

1700

AN:

33480

American (AMR)

AF:

0.175

AC:

7835

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5910

AN:

26136

East Asian (EAS)

AF:

0.370

AC:

14677

AN:

39686

South Asian (SAS)

AF:

0.280

AC:

24122

AN:

86254

European-Finnish (FIN)

AF:

0.205

AC:

10926

AN:

53382

Middle Eastern (MID)

AF:

0.200

AC:

1151

AN:

5766

European-Non Finnish (NFE)

AF:

0.187

AC:

208434

AN:

1111996

Other (OTH)

AF:

0.201

AC:

12128

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16354

32708

49061

65415

81769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7450

14900

22350

29800

37250

<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:

0.158

AC:

24110

AN:

152124

Hom.:

2357

Cov.:

AF XY:

0.163

AC XY:

12155

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0559

AC:

2322

AN:

41526

American (AMR)

AF:

0.163

AC:

2485

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

793

AN:

3472

East Asian (EAS)

AF:

0.351

AC:

1803

AN:

5140

South Asian (SAS)

AF:

0.290

AC:

1399

AN:

4816

European-Finnish (FIN)

AF:

0.213

AC:

2254

AN:

10590

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.185

AC:

12566

AN:

67984

Other (OTH)

AF:

0.166

AC:

351

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1017

2034

3052

4069

5086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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.:

4850

Bravo

AF:

0.151

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 19, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 05, 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. -

Jul 22, 2014

Eurofins Ntd Llc (ga)

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.73

CADD

Benign

0.49

(source)

DANN

Benign

0.34

PhyloP100

0.30

Mutation Taster

=96/4

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