chr2-189458803-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032168.3(WDR75):c.620C>T(p.Thr207Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
WDR75
NM_032168.3 missense
NM_032168.3 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 4.45
Genes affected
WDR75 (HGNC:25725): (WD repeat domain 75) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|
WDR75 | NM_032168.3 | c.620C>T | p.Thr207Ile | missense_variant | 7/21 | ENST00000314761.9 | |
WDR75 | NM_001303096.2 | c.428C>T | p.Thr143Ile | missense_variant | 8/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR75 | ENST00000314761.9 | c.620C>T | p.Thr207Ile | missense_variant | 7/21 | 1 | NM_032168.3 | P1 | |
WDR75 | ENST00000427960.5 | c.*1984C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/21 | 1 | ||||
WDR75 | ENST00000436347.5 | c.*384C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/22 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000408 AC: 1AN: 244848Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132326
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GnomAD4 exome AF: 0.00000344 AC: 5AN: 1454324Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2AN XY: 723204
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.620C>T (p.T207M) alteration is located in exon 7 (coding exon 7) of the WDR75 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0562);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at