chr2-19989328-C-T

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.25-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,517,914 control chromosomes in the GnomAD database, including 211,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25761 hom., cov: 33)

Exomes 𝑓: 0.52 ( 186180 hom. )

Consequence

WDR35
NM_001006657.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.10

Publications

17 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=-0.93).

BP6

Variant 2-19989328-C-T is Benign according to our data. Variant chr2-19989328-C-T is described in ClinVar as Benign. ClinVar VariationId is 256876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR35	NM_001006657.2 link	c.25-46G>A		intron_variant	Intron 1 of 27	ENST00000345530.8	NP_001006658.1	Q9P2L0-1
WDR35	NM_020779.4 link	c.25-46G>A		intron_variant	Intron 1 of 26	ENST00000281405.9	NP_065830.2	Q9P2L0-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR35	ENST00000345530.8 link	c.25-46G>A	intron_variant	Intron 1 of 27	1	NM_001006657.2	ENSP00000314444.5	Q9P2L0-1
WDR35	ENST00000281405.9 link	c.25-46G>A	intron_variant	Intron 1 of 26	1	NM_020779.4	ENSP00000281405.5	Q9P2L0-2
WDR35	ENST00000414212.5 link	n.25-46G>A	intron_variant	Intron 1 of 27	5		ENSP00000390802.1	F8WB94

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86980

AN:

151882

Hom.:

25715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.548

GnomAD2 exomes

AF:

0.541

AC:

135949

AN:

251180

AF XY:

0.540

show subpopulations

Gnomad AFR exome

AF:

0.723

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.495

Gnomad OTH exome

AF:

0.523

GnomAD4 exome

AF:

0.518

AC:

707409

AN:

1365914

Hom.:

186180

Cov.:

AF XY:

0.520

AC XY:

356256

AN XY:

685080

show subpopulations

African (AFR)

AF:

0.733

AC:

23243

AN:

31704

American (AMR)

AF:

0.523

AC:

23308

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

11770

AN:

25526

East Asian (EAS)

AF:

0.713

AC:

27955

AN:

39208

South Asian (SAS)

AF:

0.622

AC:

52386

AN:

84224

European-Finnish (FIN)

AF:

0.494

AC:

26351

AN:

53322

Middle Eastern (MID)

AF:

0.553

AC:

3079

AN:

5570

European-Non Finnish (NFE)

AF:

0.497

AC:

509400

AN:

1024580

Other (OTH)

AF:

0.523

AC:

29917

AN:

57196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

17858

35717

53575

71434

89292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14552

29104

43656

58208

72760

<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:

0.573

AC:

87086

AN:

152000

Hom.:

25761

Cov.:

AF XY:

0.574

AC XY:

42654

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.721

AC:

29908

AN:

41468

American (AMR)

AF:

0.547

AC:

8360

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1576

AN:

3466

East Asian (EAS)

AF:

0.665

AC:

3435

AN:

5162

South Asian (SAS)

AF:

0.622

AC:

3000

AN:

4824

European-Finnish (FIN)

AF:

0.489

AC:

5157

AN:

10542

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33812

AN:

67948

Other (OTH)

AF:

0.554

AC:

1167

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1848

3696

5544

7392

9240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.513

Hom.:

35035

Bravo

AF:

0.579

Asia WGS

AF:

0.663

AC:

2303

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cranioectodermal dysplasia 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Short-rib thoracic dysplasia 7 with or without polydactyly

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.090

(source)

DANN

Benign

0.70

PhyloP100

-1.1

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over