chr2-19989328-C-T

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

2

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

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
WDR35NM_001006657.2 linkc.25-46G>A intron_variant Intron 1 of 27 ENST00000345530.8 NP_001006658.1 Q9P2L0-1
WDR35NM_020779.4 linkc.25-46G>A intron_variant Intron 1 of 26 ENST00000281405.9 NP_065830.2 Q9P2L0-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR35ENST00000345530.8 linkc.25-46G>A intron_variant Intron 1 of 27 1 NM_001006657.2 ENSP00000314444.5 Q9P2L0-1
WDR35ENST00000281405.9 linkc.25-46G>A intron_variant Intron 1 of 26 1 NM_020779.4 ENSP00000281405.5 Q9P2L0-2
WDR35ENST00000414212.5 linkn.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.:
33
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.:
21
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
0
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
0
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.:
33
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
0
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
0
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
DANN
Benign
0.70
PhyloP100
-1.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3731663; hg19: chr2-20189089; COSMIC: COSV55608311; COSMIC: COSV55608311; API