Evidence Repository - Clinical Genome Resources

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:c.141C>T

CA421938891

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 264a42e6-7582-4de3-8a61-31dc2a9c7287

HGVS expressions

NM_000261.2:c.141C>T

NC_000001.11:g.171652471G>A

CM000663.2:g.171652471G>A

NC_000001.10:g.171621611G>A

CM000663.1:g.171621611G>A

NC_000001.9:g.169888234G>A

NG_008859.1:g.5163C>T

ENST00000037502.11:c.141C>T

ENST00000638471.1:c.130+11C>T

ENST00000037502.10:c.141C>T

ENST00000614688.1:c.141C>T

NM_000261.1:c.141C>T

Uncertain Significance

PS4_Supporting PM2_Supporting

PS2 PS1 PS3 BA1 PP1 PP3 PM6 PM5 PM4 BS3 BS1 BP4 BP7

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.141C>T variant in MYOC is a synonymous variant (p.Cys47=). The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.00002662 (3 alleles out of 112,692), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a CADD score (v1.6) = 11.14, which did not meet the ≤ 10 threshold for BP4 and a GERP score = 4.81 (threshold <0), not meeting BP7 and indicating conservation at this site. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 33725475), which met PS4_Supporting (≥ 2 probands). In summary, this variant met the criteria to receive a score of 2 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PS4_Supporting, PM2_Supporting

PS4_Supporting

2 probands with POAG have been reported carrying this variant (PMID: 33725475), which met PS4_Supporting (≥ 2 probands).

PM2_Supporting

The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.00002662 (3 alleles out of 112,692), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.

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 criterion was not met as PM2_Supporting has been met.

PP1

No segregations have been reported for this variant.

PP3

This is not a missense variant.

PM6

This variant has not been identified de novo.

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

This criterion was not met as PM2_Supporting has been met.

BP4

Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a CADD score (v1.6) = 11.14, which does not meet the ≤ 10 threshold for BP4.

BP7

Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a GERP score = 4.81 (threshold <0), indicating conservation at this site.

Approved on: 2022-08-28

Published on: 2022-08-28

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