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GLMN Gene Curation

GLMN Gene Curation

Owned by Andrea Oza
2024-08-14
3 min read

Gene-disease assertions not curated here (add link or write note):

Disease

Glomuvenous malformation

Disease

Glomuvenous malformation

Inheritance

Autosomal dominant

Prevalence

Orphanet

Medline Plus Genetics

 Unknown

Source:

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen dosage - sufficient for haploinsufficiency. Only 1 clinical lab in GenCC - Strong by Invitae.

Clinical Validity Scoring Notes and points

PMID: 11845407 (Brouillard 2002)

  • c.31_32delAA p.(Lys11Glufs*11) - NMD+. aka 31delAA in family Lml. 13 affected segregations. 2 VARIANT POINTS

  • c.157_161delAAGAA p.(Lys53*) - NMD+. aka 157delAAGAA in family Bl, Bln, Bt, F, Sch, Sh, T. >18 segs, 2 VARIANT POINTS

  • c.108C>A p.C36*. NMD+. in family Ba. 2 VARIANT POINTS

  • c.1355delT p.(Leu452Trpfs*24), NMD+. In family Wi. 2 VARIANT POINTS

  • c.1179_1181delCAA p.(Asn393del) - aka 1179delCAA. In family Du. 0.5 VARIANT POINTS

  • c.1547C>G p.S516*. NMD+, in family Ft. 2 VARIANT POINTS.

  • 3 points (MAX) segregations

PMID: 23801931 (Brouillard 2013) and PMID: 32538359 (Skowronek 2020) - Show replication over time with additional variants reported.

Clinical Validity Points Total

13.5

Source:

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Definitive

Source: 11845407, 23801931, 32538359

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function

 

See variants scored under clinical validity, all are NMD+ LOF.

Penetrance

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

 

Source:

Age of Onset

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

Birth to first two decades

PMID: 13707266

Severity

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

 

Clinical Features

Glomuvenous malformations - Benign cutaneous neoplasms that resemble cavernous hemangiomas. They look like raised pink or blue patch that feels bumpy to the touch. Over time, they tend to thicken and become more bluish in color, resembling a raised bruise. They can be painful. OMIM 138000 https://www.childrenshospital.org/conditions/glomuvenous-malformation

Sources:

HPO Terms

https://hpo.jax.org/app/

 

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

The GLMN gene is associated with autosomal dominant glomuvenous malformations, a type of vascular malformation characterized by the presence of smooth-muscle-like glomus cells surrounding distended vascular lumens (PMID: 11845407). They appear as raised pink or blue patches that are bumpy to the touch and may be painful. The molecular mechanism is loss of function. The glomuvenous malformations may be present at birth or develop at any age.

Case ID, Curator name, Date, Jira ticket link

AO, 56752207081211, 08.14.2024

 

 

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