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Variant: NM_000261.2(MYOC):c.1317C>T (p.Val439=)

CA1244042

806281 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: 4dcf3108-9d4a-4702-b048-b696302b2791

HGVS expressions

NM_000261.2:c.1317C>T
NM_000261.2(MYOC):c.1317C>T (p.Val439=)
NC_000001.11:g.171636123G>A
CM000663.2:g.171636123G>A
NC_000001.10:g.171605263G>A
CM000663.1:g.171605263G>A
NC_000001.9:g.169871886G>A
NG_008859.1:g.21511C>T
ENST00000037502.11:c.1317C>T
ENST00000637303.1:c.235-2507G>A
ENST00000638471.1:c.*655C>T
ENST00000037502.10:c.1317C>T
ENST00000614688.1:c.*281C>T
NM_000261.1:c.1317C>T

Likely Benign

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

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1317C>T variant in MYOC is a synonymous variant (p.Val439=). The highest minor allele frequency of this variant was in the European (Finnish) population of gnomAD (v2.1.1) = 0.003065, which met the ≥ 0.001 threshold set for BS1 (77 alleles out of 25 124, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The CADD score (v1.6) = 4.154, 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. However, BP7 was not met as this variant had a GERP score = 2.14 (threshold <0), indicating conservation at this site. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. As PM2_Supporting was not met PS4 did not apply. Additionally, this variant has not yet been identified in a proband with juvenile or primary open angle glaucoma, only in an individual with exfoliative glaucoma. 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 European (Finnish) population of gnomAD (v2.1.1) = 0.003065, which met the ≥ 0.001 threshold set for BS1 (77 alleles out of 25 124, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
BP4
The CADD score (v1.6) = 4.154, 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
This criterion was not met as BS1 has been met.
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.
BP7
Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a GERP score = 2.14 (threshold <0), indicating conservation at this site.
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.
PS4
As PM2_Supporting was not met PS4 did not apply. Additionally, this variant has not yet been identified in a proband with juvenile or primary open angle glaucoma, only in an individual with exfoliative glaucoma.
BA1
This criterion was not met as BS1 has been met.
PP3
This is not a missense variant.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
Approved on: 2022-02-21
Published on: 2022-07-11
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