chr2-19989328-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020779.4(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_020779.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

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 -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 id 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

GnomAD3 exomes

AF:

0.541

AC:

135949

AN:

251180

Hom.:

37553

AF XY:

0.540

AC XY:

73376

AN XY:

135778

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 SAS exome

AF:

0.624

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

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.713

Gnomad4 SAS exome

AF:

0.622

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.497

Gnomad4 OTH exome

AF:

0.523

GnomAD4 genome

AF:

0.573

AC:

87086

AN:

152000

Hom.:

25761

Cov.:

AF XY:

0.574

AC XY:

42654

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.721

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.665

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.489

Gnomad4 NFE

AF:

0.498

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.508

Hom.:

27386

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

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