chr1-216292367-C-G
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1
The NM_206933.4(USH2A):c.1648G>C(p.Asp550His) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D550D) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Publications
- Usher syndrome type 2Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Usher syndrome type 2AInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- retinitis pigmentosa 39Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.1648G>C | p.Asp550His | missense_variant | Exon 10 of 72 | 1 | NM_206933.4 | ENSP00000305941.3 | ||
USH2A | ENST00000366942.3 | c.1648G>C | p.Asp550His | missense_variant | Exon 10 of 21 | 1 | ENSP00000355909.3 | |||
USH2A | ENST00000674083.1 | c.1648G>C | p.Asp550His | missense_variant | Exon 10 of 73 | ENSP00000501296.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000519 AC: 13AN: 250652 AF XY: 0.0000812 show subpopulations
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461370Hom.: 0 Cov.: 30 AF XY: 0.0000550 AC XY: 40AN XY: 726994 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74314 show subpopulations
ClinVar
Submissions by phenotype
Usher syndrome type 2A Uncertain:2
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not specified Uncertain:1
proposed classification - variant undergoing re-assessment, contact laboratory -
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
not provided Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 550 of the USH2A protein (p.Asp550His). This variant is present in population databases (rs727504805, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 179343). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Retinitis pigmentosa 39 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at