chr2-189458803-C-T

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

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45
Variant links:
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]

Genome browser will be placed here

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
WDR75NM_032168.3 linkuse as main transcriptc.620C>T p.Thr207Ile missense_variant 7/21 ENST00000314761.9
WDR75NM_001303096.2 linkuse as main transcriptc.428C>T p.Thr143Ile missense_variant 8/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR75ENST00000314761.9 linkuse as main transcriptc.620C>T p.Thr207Ile missense_variant 7/211 NM_032168.3 P1
WDR75ENST00000427960.5 linkuse as main transcriptc.*1984C>T 3_prime_UTR_variant, NMD_transcript_variant 7/211
WDR75ENST00000436347.5 linkuse as main transcriptc.*384C>T 3_prime_UTR_variant, NMD_transcript_variant 8/222

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000408
AC:
1
AN:
244848
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132326
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000898
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1454324
Hom.:
0
Cov.:
29
AF XY:
0.00000277
AC XY:
2
AN XY:
723204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000223
Hom.:
0

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 submitterclinical testingAmbry GeneticsMar 07, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.70
D
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.86
MutPred
0.36
Loss of disorder (P = 0.0562);
MVP
0.26
MPC
0.68
ClinPred
0.96
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs978949559; hg19: chr2-190323529; API