DGCR6L

Chr 22

DiGeorge syndrome critical region gene 6 like

Also known as: DGCR6

NCBI Gene: 85359 ENSG00000128185 UniProt: Q9BY27 OMIM: 609459

The protein encoded by this gene may function in neural crest cell migration into the third and fourth pharyngeal pouches and shares homology with proteins involved in cell attachment and migration. This gene is located within the chromosome 22q11.2 region associated with DiGeorge syndrome, though specific disease associations with isolated DGCR6L mutations have not been established. The gene is highly tolerant to loss-of-function variants based on population data.

OMIM ResearchSummary from RefSeq, UniProt

This gene, the result of a duplication at this locus, is one of two functional genes encoding nearly identical proteins that have similar expression patterns. The product of this gene is a protein that shares homology with the Drosophila gonadal protein, expressed in gonadal tissues and germ cells, and with the human laminin gamma-1 chain that functions in cell attachment and migration. This gene is located in a region of chromosome 22 implicated in the DiGeorge syndrome, one facet of a broader collection of anomalies referred to as the CATCH 22 syndrome. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.93

OE 0.70 (0.41–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.87 (0.74–1.01)

114 obs / 131.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.41–1.27)

0≤0.351.4

Missense OE?0.87 (0.74–1.01)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 8 / 11.4Missense obs/exp: 114 / 131.2Syn Z: 0.80

Background carrier burden — how many people carry a rare variant somewhere in DGCR6L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

254 rare PASS variants

Rare truncating (LoF)

1 in 1,900

49 rare PASS variants

Rare synonymous (reference)

1 in 380

93 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DGCR6L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 1,800
South Asian	~43k	1 in 150	1 in 900
Remaining (unassigned)	~30k	1 in 190	1 in 3,300
European (Finnish)	~27k	1 in 380	1 in 4,400
Admixed American	~22k	1 in 220	1 in 3,200
African / African American	~21k	1 in 120	1 in 2,200
East Asian	~20k	1 in 160	1 in 2,100
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 450	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.