rs375083165
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_206933.4(USH2A):c.313C>T(p.Leu105Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L105L) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.313C>T | p.Leu105Phe | missense_variant | 2/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.313C>T | p.Leu105Phe | missense_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.313C>T | p.Leu105Phe | missense_variant | 2/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.313C>T | p.Leu105Phe | missense_variant | 2/21 | 1 | |||
USH2A | ENST00000674083.1 | c.313C>T | p.Leu105Phe | missense_variant | 2/73 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000382 AC: 96AN: 251014Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135648
GnomAD4 exome AF: 0.000169 AC: 247AN: 1461660Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 137AN XY: 727118
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 22, 2010 | The Leu105Phe variant in USH2A has not been reported in the literature nor previ ously identified by our laboratory. This residue is not highly conserved in mamm als and computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a hig h likelihood of impact to the protein. In addition, horse has Phenylalanine sugg esting that this variant is well tolerated at this position. In summary, the dat a suggests that this variant is more likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 25, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at