CCDC82

Genetic evidence – Published: PMID: 35373332 — One proband with homozygous NM_024725.4:c.183del; p.(Phe61Leufs*27) (frameshift, predicted null); AR inheritance; consistent neurodevelopmental phenotype; no detailed segregation reported. Case-level points (default for predicted null in AR disease) = 1.0 (AR predicted/proven null = 1.5, −0.5 downgrade for homozygosity/consanguinity); segregation = 0; case-control = 0 PMID: 40836236 — One consanguineous pedigree with two affected individuals homozygous for NM_024725.4:c.709C>T; p.(Arg237Ter) (predicted null); AR inheritance; infantile hypotonia, developmental delay, epileptic encephalopathy; segregation demonstrated in family. Case-level points (two affected with shared predicted null) = 2.0 (1.0 each after −0.5 downgrade); segregation = 1.0; case-control = 0 PMID: 28600779 — One unrelated proband homozygous for NM_024725.4:c.904G>T; p.(Asp302Tyr) (missense, non-pLoF); AR inheritance; matching neurodevelopmental phenotype; no segregation reported. Case-level points = 0.1 (AR “other variant” default); segregation = 0; case-control = 0 PMID: 34791078 — One unrelated proband homozygous for NM_024725.4:c.904G>T; p.(Asp302Tyr) (missense, non-pLoF); AR inheritance; consistent phenotype; no segregation reported. Case-level points = 0.1 (AR “other variant” default); segregation = 0; case-control = 0 Published genetic evidence total = 2.2 / 12 Genetic evidence – Our cases: Family 1 — Two affected sisters homozygous for NM_001318736.1:c.535C>T; p.(Arg179Ter) (nonsense, predicted null); AR inheritance; segregation confirmed (affected homozygous, parents and multiple siblings heterozygous carriers, additional siblings wild type); consistent neurodevelopmental phenotype with epilepsy. Case-level points = 2.0 (1.0 each after −0.5 downgrade for homozygosity/consanguinity); segregation = 0; case-control = 0 Family 2 — One proband homozygous for NM_001318736.1:c.535C>T; p.(Arg179Ter) (predicted null); consanguinity; spasticity/ataxia/GDD phenotype; no additional segregation. Case-level points = 1.0 (1.5 − 0.5); segregation = 0; case-control = 0 Family 3 — One proband homozygous for NM_001318736.1:c.709C>T; p.(Arg237Ter) (predicted null); severe congenital anomalies, seizures, early death; consanguinity; no segregation data. Case-level points = 1.0 (1.5 − 0.5); segregation = 0; case-control = 0 Family 4 — One proband homozygous for NM_001318736.1:c.910dup; p.(Glu304GlyfsTer3) (frameshift, predicted null); hypotonia and motor delay; consanguinity; no segregation data. Case-level points = 1.0 (1.5 − 0.5); segregation = 0; case-control = 0 Our cases contribution = 5.0 / 12 Total genetic evidence (published + current) = 7.2 / 12 Experimental evidence – Published: Across PMIDs 35373332, 40836236, 28600779, and 34791078, evidence is primarily human genetic with predicted loss-of-function mechanism; no demonstrated functional alteration in patient cells and no disease animal model reported Points = 0.5; Expression = 0.5 (PMID: 34791375, 35239393) Experimental evidence total = 1.0 / 6 Overall score = 8.2

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC82 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 8

CCDC82-related disorderTotal: 2

Syndromic intellectual disabilityTotal: 1

Intellectual disabilityTotal: 1

CCDC82-Related DisordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024725.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			80 clinvar	7 clinvar	1 clinvar	88
nonsense		3 clinvar	1 clinvar			4
start loss						0
frameshift	1 clinvar		4 clinvar			5
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	3	89	7	1	101

Highest pathogenic variant AF is 0.000008057029

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 155 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024725.4	RefSeq	NP_079001.2	7	MANE Select
ENST00000646818.2	Ensembl	ENSP00000496393.1	7	MANE Select
NM_001318736.2	RefSeq	NP_001305665.1	7	Standard
NM_001318737.3	RefSeq	NP_001305666.1	2	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278520
Coding exons: 7
Length: 37155
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125734
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0834	275	279	0.986	0.0000144	3661
Missense (PolyPhen)		97	109.52	0.88568		1392
Synonymous	0.348	90	94.3	0.954	0.00000469	898
Loss of Function	2.14	15	27.0	0.556	0.00000153	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00014	0.00013	rare
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.916
RVIS EVS: 0.82
RVIS percentile EVS: 88.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.553

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium