VPS26C

protein-coding

VPS26 endosomal protein sorting factor C, the group of Retriever complex

Gene summary

The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and cognitive disability. The DSCR3 (Down syndrome critical region gene 3) gene is found in this region and is predictated to contain eight exons. DSCR3 is expressed in most tissues examined. [provided by RefSeq, Jul 2008]

Previous symbols:

DSCR3

MANE transcript

NM_006052.2

Inheritance

ClinVar variants

P:1U:41B:2

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr21:37,223,420-37,267,919

External References & Databases

Ensembl (ENSG00000157538)

Transcript & Mutation Effects

hg38 • Region Span ~44.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS26C variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 2

Neurodevelopmental disorderTotal: 1

VPS26C-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006052.2. 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			2 clinvar	1 clinvar		3
missense			37 clinvar	1 clinvar		38
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	41	2	0	44

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006052.2	RefSeq	NP_006043.1	8	MANE Select
ENST00000309117.11	Ensembl	ENSP00000311399.6	8	MANE Select
NM_001331018.1	RefSeq	NP_001317947.1	5	Standard
NM_001331021.1	RefSeq	NP_001317950.1	7	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309117
Coding exons: 8
Length: 44542
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125747
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	143	186	0.770	0.0000112	1942
Missense (PolyPhen)		53	71.944	0.73668		743
Synonymous	0.439	74	79.0	0.937	0.00000554	586
Loss of Function	1.41	8	13.6	0.588	6.39e-7	170

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.120

Intolerance Scores

RVIS EVS: -0.27
RVIS percentile EVS: 34.6

Essentials

Essential (gene trap): N