Inheritance

X-linked recessive

Prevalence

 8.7 to 36.8 per 1,000

Source: NCBI - WWW Error Blocked Diagnostic

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

Clinical Validity Scoring Notes and points

Shashi 2015 PMID: 25256757 - c.1037_1059del23 p.(Glu346Glyfs*9) - variant located in the last exon, truncating, NMD- not in gnomAD. Variant found via WES. FIG 1 - The variant segregated in 6 affected males, absent 3 unaffected males, 3 unaffected obligate carrier females. Facial features in this family include coarseness, promi-nent supraorbital ridges, periorbital fullness, bulbous nose, prominentlower lip and large ear. 0.5 point + 1 point segregation

PMID: 33644862 - .1063DUP ARG355LYSFS*8, last exon, truncating but NMD-, absent gnomad. reported in one individual with unclassiified DD/ID. It was XL/maternally inherited. 0.5points

PMID: 34356170 - c.1066G>T p.G356W - variant has high MAF. reported de novo, classified as VUS in intellectual disability / autism cohort (see table S4). no points.

PMID: 33726816 - c.484_486delCCT Pro162del - table S7, no phenotype listed. No points.

PMID: 31785789 c.866-2A>T - last exon acceptor site, NMD-, phenotype is autism. no points due to common phenotype

• PMID: 15895365 - gene needed for brain development in zebrafish. Didn’t review this in detail, even if we apply full points gene curation is still limited

• PMID: 34260915 - another functional study, didn’t review in detail for interest of time, even if full points applied the gene is still limited

Clinical Validity Points Total

2 points

Clinical Validity Classification

Limited

Molecular Mechanism

Loss of function / Gain of function / Dominant Negative

Penetrance

(list source/PMID)

Source:

Age of Onset

(list source/PMID)

Severity

Clinical Features

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

Case ID, Curator name, Date, Jira ticket link