rs1191779

Variant names:

• chr2-19931423-C-A
• rs1191779
• NM_001006657.2:c.2857-14G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-19931423-C-A
• chr2-19931423-C-G
• chr2-19931423-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020779.4(WDR35):​c.2824-14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,612,746 control chromosomes in the GnomAD database, including 795,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71782 hom., cov: 31)
  • Exomes 𝑓: 1.0 (723524 hom.)
• Consequence: WDR35 NM_020779.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-19931423-C-A is Benign according to our data. Variant chr2-19931423-C-A is described in ClinVar as [Benign]. Clinvar id is 167846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-19931423-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR35	NM_001006657.2	c.2857-14G>T		intron_variant	Intron 24 of 27	ENST00000345530.8	NP_001006658.1
WDR35	NM_020779.4	c.2824-14G>T		intron_variant	Intron 23 of 26	ENST00000281405.9	NP_065830.2
WDR35	XM_011533007.3	c.1552-14G>T		intron_variant	Intron 13 of 16		XP_011531309.1
WDR35	XR_426989.4	n.2814-14G>T		intron_variant	Intron 23 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR35	ENST00000345530.8	c.2857-14G>T		intron_variant	Intron 24 of 27	1	NM_001006657.2	ENSP00000314444.5
WDR35	ENST00000281405.9	c.2824-14G>T		intron_variant	Intron 23 of 26	1	NM_020779.4	ENSP00000281405.5
WDR35	ENST00000414212.5	n.*139-14G>T		intron_variant	Intron 24 of 27	5		ENSP00000390802.1
WDR35	ENST00000445063.5	n.*1272-14G>T		intron_variant	Intron 15 of 17	2		ENSP00000390105.1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147581 AN: 152112 Hom.: 71734 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.985

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.977

GnomAD3 exomes AF: 0.990 AC: 248082 AN: 250652 Hom.: 122857 AF XY: 0.991 AC XY: 134376 AN XY: 135620

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 0.991

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.985

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.995 AC: 1453574 AN: 1460518 Hom.: 723524 Cov.: 42 AF XY: 0.995 AC XY: 723044 AN XY: 726610

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.994

Gnomad4 ASJ exome AF: 0.991

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.970 AC: 147686 AN: 152228 Hom.: 71782 Cov.: 31 AF XY: 0.971 AC XY: 72248 AN XY: 74430

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.977

Alfa AF: 0.985 Hom.: 13569

Bravo AF: 0.966

Asia WGS AF: 0.984 AC: 3408 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 13, 2017	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 26, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Cranioectodermal dysplasia 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
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 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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cranioectodermal dysplasia 2;C3279792:Short-rib thoracic dysplasia 7 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs1191779; hg19: chr2-20131184;