chr1-216046439-A-G

Variant names:

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.6317T>C(p.Ile2106Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 1,612,566 control chromosomes in the GnomAD database, including 346,400 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34553 hom., cov: 30)

Exomes 𝑓: 0.65 ( 311847 hom. )

Consequence

USH2A
NM_206933.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

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:

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 (MetaRNN=2.5621682E-6).

BP6

Variant 1-216046439-A-G is Benign according to our data. Variant chr1-216046439-A-G is described in ClinVar as [Benign]. Clinvar id is 167815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.6317T>C	p.Ile2106Thr	missense_variant	Exon 32 of 72	ENST00000307340.8	NP_996816.3	O75445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 link	c.6317T>C	p.Ile2106Thr	missense_variant	Exon 32 of 72	1	NM_206933.4	ENSP00000305941.3		O75445-1
USH2A	ENST00000674083.1 link	c.6317T>C	p.Ile2106Thr	missense_variant	Exon 32 of 73			ENSP00000501296.1		O75445-3

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101217

AN:

151670

Hom.:

34516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.653

GnomAD2 exomes

AF:

0.594

AC:

149206

AN:

251068

AF XY:

0.598

show subpopulations

Gnomad AFR exome

AF:

0.771

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.441

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.649

AC:

947361

AN:

1460778

Hom.:

311847

Cov.:

AF XY:

0.645

AC XY:

469052

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.771

AC:

25791

AN:

33446

American (AMR)

AF:

0.369

AC:

16475

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

17695

AN:

26104

East Asian (EAS)

AF:

0.444

AC:

17616

AN:

39678

South Asian (SAS)

AF:

0.510

AC:

44012

AN:

86234

European-Finnish (FIN)

AF:

0.653

AC:

34874

AN:

53390

Middle Eastern (MID)

AF:

0.637

AC:

3663

AN:

5752

European-Non Finnish (NFE)

AF:

0.673

AC:

748014

AN:

1111134

Other (OTH)

AF:

0.650

AC:

39221

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17175

34350

51525

68700

85875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.667

AC:

101298

AN:

151788

Hom.:

34553

Cov.:

AF XY:

0.659

AC XY:

48880

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.766

AC:

31707

AN:

41418

American (AMR)

AF:

0.505

AC:

7704

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

2352

AN:

3466

East Asian (EAS)

AF:

0.445

AC:

2279

AN:

5120

South Asian (SAS)

AF:

0.500

AC:

2404

AN:

4806

European-Finnish (FIN)

AF:

0.647

AC:

6821

AN:

10548

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45865

AN:

67880

Other (OTH)

AF:

0.651

AC:

1368

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1609

3218

4826

6435

8044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.663

Hom.:

152543

Bravo

AF:

0.657

TwinsUK

AF:

0.680

AC:

2523

ALSPAC

AF:

0.667

AC:

2569

ESP6500AA

AF:

0.761

AC:

3352

ESP6500EA

AF:

0.670

AC:

5758

ExAC

AF:

0.607

AC:

73632

Asia WGS

AF:

0.517

AC:

1800

AN:

3478

EpiCase

AF:

0.672

EpiControl

AF:

0.676

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inferred frequency = 157/386 (LMM data) -

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

- -

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2A

Benign:3

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 18, 2019

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

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.029

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0000026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.9

PhyloP100

1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

2.0

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.021

MPC

0.034

ClinPred

0.0022

GERP RS

5.4

Varity_R

0.029

gMVP

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

Loading publications...

chr1-216046439-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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