DGCR6L

Chr 22

DiGeorge syndrome critical region gene 6 like

Also known as: DGCR6

NCBI Gene: 85359 ENSG00000128185 UniProt: Q9BY27

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.

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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.27

Clinical Summary— DGCR6L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 VUS of 45 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

This gene — mechanism propensity

0.7325th %ile

GOF

0.83top 10%

LOF

0.2485th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	0	34
Likely Benign	2	1	3
Benign	0	0	0
Total	36	1	37

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

379 pathogenic / likely-pathogenic (of 394) ClinVar copy-number / structural variants overlap DGCR6L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →