rs34169020

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006657.2(WDR35):c.549C>T(p.Tyr183Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.0359 in 1,612,960 control chromosomes in the GnomAD database, including 2,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 227 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1824 hom. )

Consequence

WDR35
NM_001006657.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.43

Publications

9 publications found

Variant links:

Genes affected

WDR35 (HGNC:29250): (WD repeat domain 35) This gene encodes a member of the WD repeat protein family. 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Two patients with Sensenbrenner syndrome / cranioectodermal dysplasia (CED) were identified with mutations in this gene, consistent with a possible ciliary function.[provided by RefSeq, Sep 2010]

WDR35 Gene-Disease associations (from GenCC):

cranioectodermal dysplasia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, ClinGen, Ambry Genetics
short-rib thoracic dysplasia 7 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-19975551-G-A is Benign according to our data. Variant chr2-19975551-G-A is described in ClinVar as Benign. ClinVar VariationId is 333404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006657.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR35	NM_001006657.2	MANE Plus Clinical	c.549C>T	p.Tyr183Tyr	synonymous	Exon 6 of 28	NP_001006658.1
	WDR35	NM_020779.4	MANE Select	c.549C>T	p.Tyr183Tyr	synonymous	Exon 6 of 27	NP_065830.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WDR35	ENST00000345530.8	TSL:1 MANE Plus Clinical	c.549C>T	p.Tyr183Tyr	synonymous	Exon 6 of 28	ENSP00000314444.5
WDR35	ENST00000281405.9	TSL:1 MANE Select	c.549C>T	p.Tyr183Tyr	synonymous	Exon 6 of 27	ENSP00000281405.5
WDR35	ENST00000414212.5	TSL:5	n.549C>T		non_coding_transcript_exon	Exon 6 of 28	ENSP00000390802.1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5838

AN:

152036

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.0252

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0442

AC:

11061

AN:

250412

AF XY:

0.0420

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.0476

Gnomad ASJ exome

AF:

0.0699

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0201

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0420

GnomAD4 exome

AF:

0.0357

AC:

52080

AN:

1460806

Hom.:

1824

Cov.:

AF XY:

0.0352

AC XY:

25590

AN XY:

726698

show subpopulations

African (AFR)

AF:

0.0370

AC:

1237

AN:

33456

American (AMR)

AF:

0.0451

AC:

2017

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0710

AC:

1852

AN:

26092

East Asian (EAS)

AF:

0.230

AC:

9108

AN:

39632

South Asian (SAS)

AF:

0.0225

AC:

1936

AN:

86180

European-Finnish (FIN)

AF:

0.0200

AC:

1067

AN:

53364

Middle Eastern (MID)

AF:

0.0382

AC:

220

AN:

5762

European-Non Finnish (NFE)

AF:

0.0289

AC:

32136

AN:

1111274

Other (OTH)

AF:

0.0415

AC:

2507

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

2372

4745

7117

9490

11862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1368

2736

4104

5472

6840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0385

AC:

5855

AN:

152154

Hom.:

227

Cov.:

AF XY:

0.0392

AC XY:

2912

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0390

AC:

1619

AN:

41516

American (AMR)

AF:

0.0328

AC:

501

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3470

East Asian (EAS)

AF:

0.205

AC:

1063

AN:

5178

South Asian (SAS)

AF:

0.0252

AC:

121

AN:

4806

European-Finnish (FIN)

AF:

0.0166

AC:

175

AN:

10562

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0271

AC:

1845

AN:

68010

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

277

554

832

1109

1386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0323

Hom.:

Bravo

AF:

0.0428

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

EpiCase

AF:

0.0280

EpiControl

AF:

0.0295

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Cranioectodermal dysplasia 2 (1)

Cranioectodermal dysplasia 2;C3279792:Short-rib thoracic dysplasia 7 with or without polydactyly (1)

Short-rib thoracic dysplasia 7 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.4

(source)

DANN

Benign

0.62

PhyloP100

4.4

Mutation Taster

=292/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over