NM_000261.2:c.98G>A

CA1244330

1703222 (ClinVar)

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

UUID: b2497530-9cc8-4ba3-a92f-f06d7aa386cf

Approved on: 2022-08-28

Published on: 2022-08-28

HGVS expressions

NM_000261.2:c.98G>A
NC_000001.11:g.171652514C>T
CM000663.2:g.171652514C>T
NC_000001.10:g.171621654C>T
CM000663.1:g.171621654C>T
NC_000001.9:g.169888277C>T
NG_008859.1:g.5120G>A
ENST00000037502.11:c.98G>A
ENST00000638471.1:c.98G>A
ENST00000037502.10:c.98G>A
ENST00000614688.1:c.98G>A
NM_000261.1:c.98G>A

Likely Benign

• Met criteria codes: BS1 BP4

• Not Met criteria codes: PS1 PS2 PS3 PS4 PP1 PP3 PM6 PM2 PM5 PM4 BA1 BS3 BP7

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Evidence submitted by expert panel

Glaucoma VCEP

The c.98G>A variant in MYOC is a missense variant predicted to cause substitution of Arginine by Lysine at amino acid 33 (p.Arg33Lys). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.001241, which met the ≥ 0.001 threshold set for BS1 (38 alleles out of 30 610, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.055, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although a proband with primary open angle glaucoma had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant met the criteria to receive a score of -5 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1, BP4

Met criteria codes

• BS1: The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.001241, which met the ≥ 0.001 threshold set for BS1 (38 alleles out of 30 610, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
• BP4: The REVEL score = 0.055, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.

Not Met criteria codes

• PS1: An established pathogenic variant causing this same amino acid change has not been identified.
• PS2: This variant has not been identified de novo.
• PS3: No functional evidence has been found for this variant.
• PS4: Although a proband with POAG had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
• PP1: As BA1/BS1 was met, PP1 did not apply and segregations were not counted.
• PP3: This criterion was not met as BP4 has been met.
• PM6: This variant has not been identified de novo.
• PM2: This criterion was not met as BS1 has been met.
• PM5: No other missense variants at this amino acid residue have been identified.
• PM4: This variant does not cause a protein length change.
• BA1: This criterion was not met as BS1 has been met.
• BS3: No functional evidence has been found for this variant.
• BP7: This is not a synonymous or non-coding variant.