Genetic Variant USH2A:c.4252-16_4252-13delCTTT (chr1-216190379-AAAAG-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_206933.4(USH2A):c.4252-16_4252-13delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 1,597,562 control chromosomes in the GnomAD database, including 524 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 282 hom., cov: 31)

Exomes 𝑓: 0.0042 ( 242 hom. )

Consequence

USH2A
NM_206933.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.46

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-216190379-AAAAG-A is Benign according to our data. Variant chr1-216190379-AAAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 178671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-216190379-AAAAG-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.4252-16_4252-13delCTTT		intron_variant	Intron 19 of 71	ENST00000307340.8	NP_996816.3	O75445-1
USH2A	NM_007123.6 link	c.4252-16_4252-13delCTTT		intron_variant	Intron 19 of 20		NP_009054.6	O75445-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
USH2A	ENST00000307340.8 link	c.4252-16_4252-13delCTTT	intron_variant	Intron 19 of 71	1	NM_206933.4	ENSP00000305941.3	O75445-1
USH2A	ENST00000366942.3 link	c.4252-16_4252-13delCTTT	intron_variant	Intron 19 of 20	1		ENSP00000355909.3	O75445-2
USH2A	ENST00000674083.1 link	c.4252-16_4252-13delCTTT	intron_variant	Intron 19 of 72			ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5103

AN:

151604

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.00955

AC:

2339

AN:

244842

Hom.:

115

AF XY:

0.00742

AC XY:

983

AN XY:

132502

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00693

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.000501

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.000935

Gnomad OTH exome

AF:

0.00518

GnomAD4 exome

AF:

0.00421

AC:

6090

AN:

1445842

Hom.:

242

AF XY:

0.00379

AC XY:

2728

AN XY:

719300

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.00807

Gnomad4 ASJ exome

AF:

0.000661

Gnomad4 EAS exome

AF:

0.000771

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.000765

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0338

AC:

5130

AN:

151720

Hom.:

282

Cov.:

AF XY:

0.0323

AC XY:

2395

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0256

Bravo

AF:

0.0377

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 17, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

4252-16_4252-13delCTTT in Intron 19 of USH2A: This variant is not expected to h ave clinical significance because it does not alter the splice consensus sequenc e and it has been identified in 10.9% (466/4264) African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 39

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2A

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-216190379-AAAAGAAAGAAAG-AAAAGAAAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over