14-100381547-C-G

Variant names:

• chr14-100381547-C-G
• rs375660046
• NM_001161476.3:c.623C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001161476.3(WDR25):​c.623C>G​(p.Pro208Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: WDR25 NM_001161476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.542
• Publications: 2 publications found

Genes affected

WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.094812095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR25	NM_001161476.3	MANE Select	c.623C>G	p.Pro208Arg	missense	Exon 2 of 7	NP_001154948.1	A0A384NPW5
	WDR25	NM_001350947.2		c.623C>G	p.Pro208Arg	missense	Exon 2 of 7	NP_001337876.1	A0A384NPW5
	WDR25	NM_001350948.2		c.623C>G	p.Pro208Arg	missense	Exon 2 of 7	NP_001337877.1	Q64LD2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR25	ENST00000402312.8	TSL:2 MANE Select	c.623C>G	p.Pro208Arg	missense	Exon 2 of 7	ENSP00000385540.3	Q64LD2-1
	WDR25	ENST00000335290.10	TSL:1	c.623C>G	p.Pro208Arg	missense	Exon 2 of 7	ENSP00000334148.6	Q64LD2-1
	WDR25	ENST00000554175.5	TSL:1	c.623C>G	p.Pro208Arg	missense	Exon 2 of 3	ENSP00000450727.1	G3V2K8

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 32 AN: 251194 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000238 AC: 348 AN: 1461764 Hom.: 0 Cov.: 93 AF XY: 0.000242 AC XY: 176 AN XY: 727186

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.000134 AC: 6 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000290 AC: 323 AN: 1111912

Other (OTH) AF: 0.000282 AC: 17 AN: 60390

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74434

African (AFR) AF: 0.0000241 AC: 1 AN: 41562

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.000102

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.54
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.19
Sift	Benign	0.099	T
Sift4G	Uncertain	0.055	T
Polyphen		0.95	P
Vest4		0.30
MVP		0.18
MPC		0.33
ClinPred		0.25	T
GERP RS		4.8
PromoterAI		0.014	Neutral
Varity_R		0.15
gMVP		0.17
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs375660046; hg19: chr14-100847884;