rs546494522
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_206933.4(USH2A):c.15546C>T(p.Asn5182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,613,982 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 6 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.777
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 1-215625844-G-A is Benign according to our data. Variant chr1-215625844-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 179122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.777 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.15546C>T | p.Asn5182= | synonymous_variant | 72/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.15546C>T | p.Asn5182= | synonymous_variant | 72/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.15618C>T | p.Asn5206= | synonymous_variant | 73/73 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000788 AC: 198AN: 251400Hom.: 3 AF XY: 0.000979 AC XY: 133AN XY: 135864
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GnomAD4 exome AF: 0.000410 AC: 599AN: 1461768Hom.: 6 Cov.: 31 AF XY: 0.000554 AC XY: 403AN XY: 727190
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74414
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 15, 2013 | Asn5182Asn in Exon 72 of USH2A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and it is not locate d within the splice consensus sequence. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 12, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Usher syndrome type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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