chr2-19935522-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020779.4(WDR35):c.2496A>G(p.Glu832Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,612,456 control chromosomes in the GnomAD database, including 162,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16169 hom., cov: 32)

Exomes 𝑓: 0.44 ( 146678 hom. )

Consequence

WDR35
NM_020779.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.74

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-19935522-T-C is Benign according to our data. Variant chr2-19935522-T-C is described in ClinVar as [Benign]. Clinvar id is 256877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-19935522-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR35	NM_001006657.2 link	c.2529A>G	p.Glu843Glu	synonymous_variant	Exon 22 of 28	ENST00000345530.8	NP_001006658.1	Q9P2L0-1
WDR35	NM_020779.4 link	c.2496A>G	p.Glu832Glu	synonymous_variant	Exon 21 of 27	ENST00000281405.9	NP_065830.2	Q9P2L0-2
WDR35	XM_011533007.3 link	c.1224A>G	p.Glu408Glu	synonymous_variant	Exon 11 of 17		XP_011531309.1
WDR35	XR_426989.4 link	n.2586A>G		non_coding_transcript_exon_variant	Exon 21 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR35	ENST00000345530.8 link	c.2529A>G	p.Glu843Glu	synonymous_variant	Exon 22 of 28	1	NM_001006657.2	ENSP00000314444.5		Q9P2L0-1
WDR35	ENST00000281405.9 link	c.2496A>G	p.Glu832Glu	synonymous_variant	Exon 21 of 27	1	NM_020779.4	ENSP00000281405.5		Q9P2L0-2

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69538

AN:

151826

Hom.:

16146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.473

AC:

118574

AN:

250584

Hom.:

28896

AF XY:

0.476

AC XY:

64476

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.444

AC:

647908

AN:

1460512

Hom.:

146678

Cov.:

AF XY:

0.447

AC XY:

325126

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.477

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.696

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.458

AC:

69613

AN:

151944

Hom.:

16169

Cov.:

AF XY:

0.463

AC XY:

34417

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.639

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.424

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.425

Hom.:

21700

Bravo

AF:

0.457

Asia WGS

AF:

0.622

AC:

2159

AN:

3474

EpiCase

AF:

0.425

EpiControl

AF:

0.426

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Oct 26, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cranioectodermal dysplasia 2

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Short-rib thoracic dysplasia 7 with or without polydactyly

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over