rs74766738
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_206933.4(USH2A):c.5857+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,608,520 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 59 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 52 hom. )
Consequence
USH2A
NM_206933.4 intron
NM_206933.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0590
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 1-216072872-T-G is Benign according to our data. Variant chr1-216072872-T-G is described in ClinVar as [Benign]. Clinvar id is 263276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-216072872-T-G is described in Lovd as [Benign]. Variant chr1-216072872-T-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.5857+17A>C | intron_variant | ENST00000307340.8 | |||
USH2A-AS2 | NR_125992.1 | n.136+272T>G | intron_variant, non_coding_transcript_variant | ||||
USH2A-AS2 | NR_125993.1 | n.136+272T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.5857+17A>C | intron_variant | 1 | NM_206933.4 | P1 | |||
USH2A-AS2 | ENST00000446411.5 | n.136+272T>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0155 AC: 2357AN: 152096Hom.: 58 Cov.: 32
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GnomAD3 exomes AF: 0.00387 AC: 970AN: 250512Hom.: 20 AF XY: 0.00265 AC XY: 359AN XY: 135350
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GnomAD4 exome AF: 0.00157 AC: 2283AN: 1456306Hom.: 52 Cov.: 29 AF XY: 0.00129 AC XY: 934AN XY: 724930
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GnomAD4 genome ? AF: 0.0155 AC: 2364AN: 152214Hom.: 59 Cov.: 32 AF XY: 0.0149 AC XY: 1106AN XY: 74406
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 14, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Retinitis pigmentosa 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Usher syndrome type 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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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