rs75698489
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_206933.4(USH2A):c.5932C>T(p.Pro1978Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000312 in 1,613,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1978H) has been classified as Uncertain significance.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.5932C>T | p.Pro1978Ser | missense_variant | 30/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.5932C>T | p.Pro1978Ser | missense_variant | 30/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.5932C>T | p.Pro1978Ser | missense_variant | 30/73 |
Frequencies
GnomAD3 genomes ? AF: 0.00185 AC: 282AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000438 AC: 110AN: 251296Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135820
GnomAD4 exome AF: 0.000150 AC: 219AN: 1461734Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 88AN XY: 727172
GnomAD4 genome ? AF: 0.00187 AC: 285AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00172 AC XY: 128AN XY: 74408
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 03, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Pro1978Ser in Exon 30 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.5% (20/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs75698489). - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 06, 2024 | Variant summary: USH2A c.5932C>T (p.Pro1978Ser) results in a non-conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 1613916 control chromosomes in the gnomAD database (v4.0.0), including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.00031 vs 0.011). One study utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants has classified this variant as benign (Shearer_2014). The following publication have been ascertained in the context of this evaluation (PMID: 25262649). ClinVar contains an entry for this variant (Variation ID: 178652). Based on the evidence outlined above, the variant was classified as likely benign. - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 11, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2020 | This variant is associated with the following publications: (PMID: 25262649, 20507924) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Usher syndrome type 2A Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 08, 2020 | - - |
Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
USH2A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at