Variant 2-19911243-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001006657.2(WDR35):c.*2315G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,264 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 16 hom., cov: 33)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

WDR35
NM_001006657.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.295

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=-0.89).

BP6

Variant 2-19911243-C-G is Benign according to our data. Variant chr2-19911243-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 895898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
WDR35	NM_001006657.2 linkuse as main transcript	c.*2315G>C	3_prime_UTR_variant	28/28	ENST00000345530.8
WDR35	NM_020779.4 linkuse as main transcript	c.*2315G>C	3_prime_UTR_variant	27/27	ENST00000281405.9
WDR35	XM_011533007.3 linkuse as main transcript	c.*2315G>C	3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR35	ENST00000281405.9 linkuse as main transcript	c.*2315G>C		3_prime_UTR_variant	27/27	1	NM_020779.4	P3	Q9P2L0-2
WDR35	ENST00000345530.8 linkuse as main transcript	c.*2315G>C		3_prime_UTR_variant	28/28	1	NM_001006657.2	A1	Q9P2L0-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2084

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.0417

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0625

GnomAD4 genome

AF:

0.0137

AC:

2082

AN:

152240

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

982

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00325

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.00736

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cranioectodermal dysplasia 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Short-rib thoracic dysplasia 7 with or without polydactyly

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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