rs12404427

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_206933.4(USH2A):c.7506G>A(p.Pro2502Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,613,400 control chromosomes in the GnomAD database, including 6,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 470 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5609 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.03

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:

ENSG00000229242 (HGNC:):

ENSG00000229242 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-215900163-C-T is Benign according to our data. Variant chr1-215900163-C-T is described in ClinVar as [Benign]. Clinvar id is 48584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215900163-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 72	ENST00000307340.8	NP_996816.3	O75445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USH2A	ENST00000307340.8 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 72	1	NM_206933.4	ENSP00000305941.3	O75445-1
USH2A	ENST00000674083.1 link	c.7506G>A	p.Pro2502Pro	synonymous_variant	Exon 40 of 73			ENSP00000501296.1	O75445-3
ENSG00000229242	ENST00000414995.1 link	n.61-562C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0755

AC:

11471

AN:

151954

Hom.:

470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0537

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0835

Gnomad OTH

AF:

0.0632

GnomAD3 exomes

AF:

0.0684

AC:

17142

AN:

250672

Hom.:

694

AF XY:

0.0676

AC XY:

9154

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.0411

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0567

Gnomad FIN exome

AF:

0.0519

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0835

AC:

121987

AN:

1461328

Hom.:

5609

Cov.:

AF XY:

0.0823

AC XY:

59840

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.0916

Gnomad4 ASJ exome

AF:

0.0393

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.0582

Gnomad4 FIN exome

AF:

0.0521

Gnomad4 NFE exome

AF:

0.0915

Gnomad4 OTH exome

AF:

0.0740

GnomAD4 genome

AF:

0.0755

AC:

11478

AN:

152072

Hom.:

470

Cov.:

AF XY:

0.0736

AC XY:

5473

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0816

Gnomad4 AMR

AF:

0.0843

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0537

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0835

Gnomad4 OTH

AF:

0.0621

Alfa

AF:

0.0769

Hom.:

628

Bravo

AF:

0.0760

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.0751

EpiControl

AF:

0.0759

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 07, 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. -

PreventionGenetics, part of Exact Sciences

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

- -

Apr 05, 2013

Eurofins Ntd Llc (ga)

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

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

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

-0.53

CADD

Benign

1.8

DANN

Benign

0.81

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

LitVar

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

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