rs746128772
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong
The NM_001006657.2(WDR35):c.3378G>A(p.Leu1126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L1126L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001006657.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR35 | NM_001006657.2 | c.3378G>A | p.Leu1126= | synonymous_variant | 27/28 | ENST00000345530.8 | |
WDR35 | NM_020779.4 | c.3345G>A | p.Leu1115= | synonymous_variant | 26/27 | ENST00000281405.9 | |
WDR35 | XM_011533007.3 | c.2073G>A | p.Leu691= | synonymous_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR35 | ENST00000345530.8 | c.3378G>A | p.Leu1126= | synonymous_variant | 27/28 | 1 | NM_001006657.2 | A1 | |
WDR35 | ENST00000281405.9 | c.3345G>A | p.Leu1115= | synonymous_variant | 26/27 | 1 | NM_020779.4 | P3 | |
WDR35 | ENST00000414212.5 | c.*660G>A | 3_prime_UTR_variant, NMD_transcript_variant | 27/28 | 5 | ||||
WDR35 | ENST00000445063.5 | c.*1570-346G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251284Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727182
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cranioectodermal dysplasia 2;C3279792:Short-rib thoracic dysplasia 7 with or without polydactyly Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2023 | This variant has been observed in individual(s) with Ellis-van Creveld syndrome and/or Sensenbrenner syndrome (PMID: 25908617, 33606107). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in skipping of exon 27 and introduces a premature termination codon (PMID: 25908617). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 570668). This variant is present in population databases (rs746128772, gnomAD 0.004%). This sequence change affects codon 1126 of the WDR35 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the WDR35 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. - |
Cranioectodermal dysplasia 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 26, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at