Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document

Variant: NM_000261.2(MYOC):c.114G>A (p.Arg38=)

CA1244327

293723 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e16189ab-f8f5-4564-a159-b013306db86c

HGVS expressions

NM_000261.2:c.114G>A
NM_000261.2(MYOC):c.114G>A (p.Arg38=)
NC_000001.11:g.171652498C>T
CM000663.2:g.171652498C>T
NC_000001.10:g.171621638C>T
CM000663.1:g.171621638C>T
NC_000001.9:g.169888261C>T
NG_008859.1:g.5136G>A
ENST00000037502.11:c.114G>A
ENST00000638471.1:c.114G>A
ENST00000037502.10:c.114G>A
ENST00000614688.1:c.114G>A
NM_000261.1:c.114G>A

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 13
PM6 PM2 PM5 PM4 BS3 BS1 PS4 PS2 PS1 PS3 BA1 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.114G>A variant in MYOC is a synonymous variant (p.Arg38=). The highest minor allele frequency of this variant was in the Ashkenazi Jewish population of gnomAD (v2.1.1) = 0.0007944 (8 alleles out of 10,070), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). This variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), with a CADD score (v1.6) = 6.60 which met the ≤ 10 threshold for BP4, and the GERP score = -7.95 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests 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.This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma. Additionally, as PM2_Supporting was not met, PS4 did not apply. In summary, this variant met the criteria to receive a score of -2 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): BP4, BP7
Met criteria codes
BP7
This synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2) and had a GERP score = -7.95 (threshold <0), indicating a lack of conservation at this site.
BP4
The CADD score (v1.6) = 6.600, which met the ≤ 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), suggesting that the variant does not impact MYOC function.
Not Met criteria codes
PM6
This variant has not been identified de novo.
PM2
The highest minor allele frequency of this variant was in the Ashkenazi Jewish population of gnomAD (v2.1.1) = 0.0007944 (8 alleles out of 10,070), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.
PM5
This is not a missense variant.
PM4
This variant does not cause a protein length change.
BS3
No functional evidence has been found for this variant.
BS1
The highest minor allele frequency of this variant was in the Ashkenazi Jewish population of gnomAD (v2.1.1) = 0.0007944 (8 alleles out of 10,070), which did not meet the ≥ 0.001 threshold set for BS1.
PS4
This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma. Additionally, as PM2_Supporting was not met, PS4 did not apply.
PS2
This variant has not been identified de novo.
PS1
This variant does not involve an amino acid change.
PS3
No functional evidence has been found for this variant.
BA1
This variant did not meet the ≥ 0.01 minor allele frequency threshold in gnomAD (v2.1.1).
PP1
No segregations have been reported for this variant.
PP3
This is not a missense variant.
Approved on: 2023-08-08
Published on: 2023-08-08
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.