2-19931423-C-G

Position:

• chr2-19931423-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001006657.2(WDR35):​c.2857-14G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: WDR35 NM_001006657.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR35	NM_001006657.2	c.2857-14G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000345530.8	NP_001006658.1
WDR35	NM_020779.4	c.2824-14G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000281405.9	NP_065830.2
WDR35	XM_011533007.3	c.1552-14G>C		splice_polypyrimidine_tract_variant, intron_variant			XP_011531309.1
WDR35	XR_426989.4	n.2814-14G>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR35	ENST00000281405.9	c.2824-14G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020779.4	ENSP00000281405	P3
WDR35	ENST00000345530.8	c.2857-14G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001006657.2	ENSP00000314444	A1
WDR35	ENST00000414212.5	c.*139-14G>C		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000390802
WDR35	ENST00000445063.5	c.*1272-14G>C		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2		ENSP00000390105

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.066
DANN	Benign	0.21

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;