rs1191778

Positions:

• chr2-19931318-T-A
• chr2-19931318-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001006657.2(WDR35):​c.2948A>T​(p.Glu983Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E983G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: WDR35 NM_001006657.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR35	NM_001006657.2	c.2948A>T	p.Glu983Val	missense_variant	25/28	ENST00000345530.8
WDR35	NM_020779.4	c.2915A>T	p.Glu972Val	missense_variant	24/27	ENST00000281405.9
WDR35	XM_011533007.3	c.1643A>T	p.Glu548Val	missense_variant	14/17
WDR35	XR_426989.4	n.2905A>T		non_coding_transcript_exon_variant	24/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR35	ENST00000345530.8	c.2948A>T	p.Glu983Val	missense_variant	25/28	1	NM_001006657.2	A1
WDR35	ENST00000281405.9	c.2915A>T	p.Glu972Val	missense_variant	24/27	1	NM_020779.4	P3
WDR35	ENST00000414212.5	c.*230A>T		3_prime_UTR_variant, NMD_transcript_variant	25/28	5
WDR35	ENST00000445063.5	c.*1363A>T		3_prime_UTR_variant, NMD_transcript_variant	16/18	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	0.038
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.13	D
MutationTaster	Benign	0.0000026	P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.29
Sift	Benign	0.058	T;T
Sift4G	Uncertain	0.051	T;T
Polyphen		0.35	B;B
Vest4		0.60
MutPred		0.45		.;Loss of disorder (P = 0.0138);
MVP		0.58
MPC		0.42
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-20131079;