chr1-216422337-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_206933.4(USH2A):c.-1C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000143 in 1,613,482 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
USH2A
NM_206933.4 5_prime_UTR
NM_206933.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.49
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.-1C>G | 5_prime_UTR_variant | 2/72 | ENST00000307340.8 | ||
USH2A | NM_007123.6 | c.-1C>G | 5_prime_UTR_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.-1C>G | 5_prime_UTR_variant | 2/72 | 1 | NM_206933.4 | P1 | ||
USH2A | ENST00000366942.3 | c.-1C>G | 5_prime_UTR_variant | 2/21 | 1 | ||||
USH2A | ENST00000674083.1 | c.-1C>G | 5_prime_UTR_variant | 2/73 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249004Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134870
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461418Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 726998
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74256
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 06, 2013 | The -1C>G variant in USH2A has not been reported in individuals with hearing los s nor previously identified by our laboratory. Data from large population studie s is insufficient to assess the frequency of this variant. This variant is locat ed in the 5'UTR at the -1 nucleotide position and is conserved across species; t hough this information is insufficient to determine pathogenicity. Although we c annot rule out a deleterious impact on the regulation of splicing or translation of USH2A, to date no disease-causing variants have been found in this region of the transcript. In summary, additional information is needed to determine the c linical significance of this variant. - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
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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