rs2234926
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000261.2(MYOC):c.227G>A(p.Arg76Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,274 control chromosomes in the GnomAD database, including 18,563 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Consequence
NM_000261.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOC | NM_000261.2 | c.227G>A | p.Arg76Lys | missense_variant | 1/3 | ENST00000037502.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOC | ENST00000037502.11 | c.227G>A | p.Arg76Lys | missense_variant | 1/3 | 1 | NM_000261.2 | P1 | |
MYOC | ENST00000638471.1 | c.130+97G>A | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.108 AC: 16415AN: 152108Hom.: 1252 Cov.: 32
GnomAD3 exomes AF: 0.147 AC: 37010AN: 251002Hom.: 3720 AF XY: 0.160 AC XY: 21758AN XY: 135594
GnomAD4 exome AF: 0.141 AC: 206715AN: 1461048Hom.: 17310 Cov.: 33 AF XY: 0.148 AC XY: 107803AN XY: 726668
GnomAD4 genome ? AF: 0.108 AC: 16424AN: 152226Hom.: 1253 Cov.: 32 AF XY: 0.112 AC XY: 8337AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 18449353, 17361544, 28792703, 22449891, 15025728, 27884173, 21168818, 23029558, 14688426, 23517641, 16466712) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2016 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 10, 2014 | - - |
Glaucoma 1, open angle, A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Glaucoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Glaucoma of childhood Benign:1
Benign, reviewed by expert panel | curation | ClinGen Glaucoma Variant Curation Expert Panel | Mar 05, 2022 | The c.227G>A variant in MYOC is a missense variant predicted to cause substitution of Arginine by Lysine at amino acid 76 (p.Arg76Lys). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.3468, which met the >= 0.01 threshold set for BA1 (10,613 alleles out of 30,602, meeting the threshold of >= 5 of at least 2,000 observed alleles). The REVEL score = 0.203, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<= 0.15), predicting a damaging or benign impact on MYOC function. Previous studies (PMIDs: 16466712 and 35196929) demonstrated that the Arg76Lys protein had similar solubility and secretion levels to wild type myocilin protein and met the OddsPath threshold for BS3_Moderate (< 0.23), indicating that this variant did not impact protein function. As BA1 was met, PP1 did not apply and segregations were not counted. Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BA1, BS3_Moderate. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at