Variant 1-215741541-GAA-GAAA details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_206933.4(USH2A):c.11549-5_11549-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 928,684 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1 hom. )

Consequence

USH2A
NM_206933.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.396

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 -16 ACMG points.

BP6

Variant 1-215741541-G-GA is Benign according to our data. Variant chr1-215741541-G-GA is described in ClinVar as [Benign]. Clinvar id is 198307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0617 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.11549-5_11549-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 linkuse as main transcript	c.11549-5_11549-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_206933.4	ENSP00000305941	P1	O75445-1
USH2A	ENST00000674083.1 linkuse as main transcript	c.11549-5_11549-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000501296		O75445-3

Frequencies

GnomAD3 genomes

AF:

0.000931

AC:

129

AN:

138634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000862

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000450

Gnomad FIN

AF:

0.00533

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000880

Gnomad OTH

AF:

0.00106

GnomAD3 exomes

AF:

0.0572

AC:

6751

AN:

118084

Hom.:

AF XY:

0.0557

AC XY:

3518

AN XY:

63212

show subpopulations

Gnomad AFR exome

AF:

0.0416

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.0900

Gnomad EAS exome

AF:

0.0598

Gnomad SAS exome

AF:

0.0693

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0741

GnomAD4 exome

AF:

0.0507

AC:

40031

AN:

789990

Hom.:

Cov.:

AF XY:

0.0506

AC XY:

19779

AN XY:

391068

show subpopulations

Gnomad4 AFR exome

AF:

0.0578

Gnomad4 AMR exome

AF:

0.0643

Gnomad4 ASJ exome

AF:

0.0698

Gnomad4 EAS exome

AF:

0.0588

Gnomad4 SAS exome

AF:

0.0637

Gnomad4 FIN exome

AF:

0.0558

Gnomad4 NFE exome

AF:

0.0479

Gnomad4 OTH exome

AF:

0.0550

GnomAD4 genome

AF:

0.000937

AC:

130

AN:

138694

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

66854

show subpopulations

Gnomad4 AFR

AF:

0.000448

Gnomad4 AMR

AF:

0.000860

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000451

Gnomad4 FIN

AF:

0.00533

Gnomad4 NFE

AF:

0.000880

Gnomad4 OTH

AF:

0.00105

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Usher syndrome type 2A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 25, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 29, 2014

- -

Retinitis pigmentosa 39

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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