rs397518028
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_206933.4(USH2A):āc.6969A>Cā(p.Arg2323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.270
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 1-215965468-T-G is Benign according to our data. Variant chr1-215965468-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 48574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.27 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.6969A>C | p.Arg2323= | synonymous_variant | 37/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.6969A>C | p.Arg2323= | synonymous_variant | 37/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.6969A>C | p.Arg2323= | synonymous_variant | 37/73 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251000Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135658
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461372Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726984
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 07, 2011 | The Arg2323Arg variant in USH2A is not expected to have clinical significance be cause it does not alter an amino acid residue and is not located near a splice j unction. - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Nov 16, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2022 | - - |
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