rs41277194
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The ENST00000307340.8(USH2A):āc.9296A>Gā(p.Asn3099Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0302 in 1,613,804 control chromosomes in the GnomAD database, including 883 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.040 ( 145 hom., cov: 32)
Exomes š: 0.029 ( 738 hom. )
Consequence
USH2A
ENST00000307340.8 missense
ENST00000307340.8 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.10
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
PM1
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity USH2A_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.0027686954).
BP6
Variant 1-215838066-T-C is Benign according to our data. Variant chr1-215838066-T-C is described in ClinVar as [Benign]. Clinvar id is 48620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215838066-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.9296A>G | p.Asn3099Ser | missense_variant | 47/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.9296A>G | p.Asn3099Ser | missense_variant | 47/72 | 1 | NM_206933.4 | ENSP00000305941 | P1 | |
USH2A | ENST00000674083.1 | c.9296A>G | p.Asn3099Ser | missense_variant | 47/73 | ENSP00000501296 |
Frequencies
GnomAD3 genomes AF: 0.0395 AC: 6013AN: 152120Hom.: 142 Cov.: 32
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GnomAD3 exomes AF: 0.0276 AC: 6943AN: 251320Hom.: 104 AF XY: 0.0269 AC XY: 3649AN XY: 135812
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GnomAD4 exome AF: 0.0292 AC: 42658AN: 1461566Hom.: 738 Cov.: 31 AF XY: 0.0286 AC XY: 20798AN XY: 727088
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GnomAD4 genome AF: 0.0396 AC: 6028AN: 152238Hom.: 145 Cov.: 32 AF XY: 0.0392 AC XY: 2915AN XY: 74452
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ESP6500AA
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307
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 11, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 24, 2009 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 27, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Usher syndrome type 2A Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at