rs373694614
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_206933.4(USH2A):c.13857A>G(p.Ser4619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,614,142 control chromosomes in the GnomAD database, including 4 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 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 3 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.66
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 1-215671248-T-C is Benign according to our data. Variant chr1-215671248-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215671248-T-C is described in Lovd as [Likely_benign]. Variant chr1-215671248-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.66 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.13857A>G | p.Ser4619= | synonymous_variant | 64/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.13857A>G | p.Ser4619= | synonymous_variant | 64/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.13857A>G | p.Ser4619= | synonymous_variant | 64/73 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152156Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000733 AC: 184AN: 251046Hom.: 0 AF XY: 0.00101 AC XY: 137AN XY: 135662
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GnomAD4 exome AF: 0.000369 AC: 539AN: 1461868Hom.: 3 Cov.: 31 AF XY: 0.000527 AC XY: 383AN XY: 727234
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 28, 2015 | p.Ser4619Ser in exon 64 of USH2A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.6% (94/16510) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs373694614). - |
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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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