chr2-19931423-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09
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]

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ACMG classification

Classification made for transcript

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
WDR35NM_001006657.2 linkuse as main transcriptc.2857-14G>C splice_polypyrimidine_tract_variant, intron_variant ENST00000345530.8 NP_001006658.1
WDR35NM_020779.4 linkuse as main transcriptc.2824-14G>C splice_polypyrimidine_tract_variant, intron_variant ENST00000281405.9 NP_065830.2
WDR35XM_011533007.3 linkuse as main transcriptc.1552-14G>C splice_polypyrimidine_tract_variant, intron_variant XP_011531309.1
WDR35XR_426989.4 linkuse as main transcriptn.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
WDR35ENST00000281405.9 linkuse as main transcriptc.2824-14G>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_020779.4 ENSP00000281405 P3Q9P2L0-2
WDR35ENST00000345530.8 linkuse as main transcriptc.2857-14G>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_001006657.2 ENSP00000314444 A1Q9P2L0-1
WDR35ENST00000414212.5 linkuse as main transcriptc.*139-14G>C splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 5 ENSP00000390802
WDR35ENST00000445063.5 linkuse as main transcriptc.*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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1191779; hg19: chr2-20131184; API