Variant 1-215970606-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr1-215970606-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
USH2A	NM_206933.4 linkuse as main transcript	c.6957+19A>G		intron_variant		ENST00000307340.8	NP_996816.3	O75445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 linkuse as main transcript	c.6957+19A>G		intron_variant		1	NM_206933.4	ENSP00000305941.3		O75445-1
USH2A	ENST00000674083.1 linkuse as main transcript	c.6957+19A>G		intron_variant				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

GnomAD3 exomes

AF:

0.0856

AC:

21454

AN:

250630

Hom.:

1083

AF XY:

0.0854

AC XY:

11560

AN XY:

135434

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 SAS exome

AF:

0.0902

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

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0725

Gnomad4 EAS exome

AF:

0.000806

Gnomad4 SAS exome

AF:

0.0931

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0999

Gnomad4 OTH exome

AF:

0.0911

GnomAD4 genome

AF:

0.0962

AC:

14646

AN:

152170

Hom.:

759

Cov.:

AF XY:

0.0955

AC XY:

7107

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0818

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.0844

Gnomad4 FIN

AF:

0.0704

Gnomad4 NFE

AF:

0.0973

Gnomad4 OTH

AF:

0.0919

Alfa

AF:

0.0925

Hom.:

185

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2011	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Usher syndrome type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.60

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