1-215970606-T-C

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.6957+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 1,613,192 control chromosomes in the GnomAD database, including 7,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 759 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7157 hom. )

Consequence

USH2A
NM_206933.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.66

Publications

8 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=-0.67).

BP6

Variant 1-215970606-T-C is Benign according to our data. Variant chr1-215970606-T-C is described in ClinVar as [Benign]. Clinvar id is 137896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.6957+19A>G		intron_variant	Intron 36 of 71	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.6957+19A>G		intron_variant	Intron 36 of 71	1	NM_206933.4	ENSP00000305941.3		O75445-1
USH2A	ENST00000674083.1 link	c.6957+19A>G		intron_variant	Intron 36 of 72			ENSP00000501296.1		O75445-3

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14620

AN:

152052

Hom.:

754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0849

Gnomad FIN

AF:

0.0704

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0973

Gnomad OTH

AF:

0.0929

GnomAD2 exomes

AF:

0.0856

AC:

21454

AN:

250630

AF XY:

0.0854

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0739

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0911

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.0954

AC:

139450

AN:

1461022

Hom.:

7157

Cov.:

AF XY:

0.0953

AC XY:

69262

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.121

AC:

4029

AN:

33430

American (AMR)

AF:

0.107

AC:

4771

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.0725

AC:

1894

AN:

26112

East Asian (EAS)

AF:

0.000806

AC:

AN:

39682

South Asian (SAS)

AF:

0.0931

AC:

8028

AN:

86246

European-Finnish (FIN)

AF:

0.0687

AC:

3667

AN:

53384

Middle Eastern (MID)

AF:

0.0856

AC:

493

AN:

5760

European-Non Finnish (NFE)

AF:

0.0999

AC:

111038

AN:

1111436

Other (OTH)

AF:

0.0911

AC:

5498

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6386

12772

19158

25544

31930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4128

8256

12384

16512

20640

<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:

0.0962

AC:

14646

AN:

152170

Hom.:

759

Cov.:

AF XY:

0.0955

AC XY:

7107

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.113

AC:

4712

AN:

41542

American (AMR)

AF:

0.106

AC:

1619

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0818

AC:

284

AN:

3470

East Asian (EAS)

AF:

0.00136

AC:

AN:

5166

South Asian (SAS)

AF:

0.0844

AC:

407

AN:

4824

European-Finnish (FIN)

AF:

0.0704

AC:

747

AN:

10606

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0973

AC:

6617

AN:

68014

Other (OTH)

AF:

0.0919

AC:

194

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

664

1328

1992

2656

3320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0936

Hom.:

277

Bravo

AF:

0.0964

Asia WGS

AF:

0.0490

AC:

170

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 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. -

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: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

-0.67

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.7

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