WDR49

Chr 3

WD repeat domain 49

Also known as: CFAP337

NCBI Gene: 151790 ENSG00000174776 UniProt: Q8IV35

This gene encodes a member of the WD repeat protein family with nine WD repeats. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.49

OE 0.91 (0.68–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.44Z-score

OE missense 1.07 (0.98–1.16)

372 obs / 348.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.68–1.23)

0≤0.351.4

Missense OE?1.07 (0.98–1.16)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 31 / 34.1Missense obs/exp: 372 / 348.9Syn Z: 1.35

Background carrier burden — how many people carry a rare variant somewhere in WDR49?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,332 rare PASS variants

Rare truncating (LoF)

1 in 310

257 rare PASS variants

Rare synonymous (reference)

1 in 150

456 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for WDR49. 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 42	1 in 450
South Asian	~43k	1 in 30	1 in 330
Remaining (unassigned)	~30k	1 in 29	1 in 180
European (Finnish)	~27k	1 in 150	1 in 1,100
Admixed American	~22k	1 in 32	1 in 240
African / African American	~21k	1 in 35	1 in 200
East Asian	~20k	1 in 54	1 in 220
Ashkenazi Jewish	~13k	1 in 200	1 in 360
Middle Eastern	~2,884	1 in 40	1 in 300

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 18 coding exons well covered in gnomAD exomes; exons 3, 11, 17 marginal. Genomes: all 18.? see exons ↓